Chemosensory gene family encoding gustatory and olfactory receptors and uses thereof

ABSTRACT

This invention provides an isolated nucleic acid encoding an insect gustatory or odorant receptor. This invention provides a nucleic acid of at least 12 nucleotides capable of specifically hybridizing with a nucleic acid encoding an insect gustatory or odorant receptor. This invention also provides a purified, insect gustatory or odorant receptor. This invention provides an antibody capable of specifically binding to an insect gustatory or odorant receptor. This invention provides a method of identifying a compound capable of specifically binding to, activating, or inhibiting the activity of an insect gustatory or odorant receptor. This invention also provides methods of controlling insect populations.

[0001] This application claims the benefit of U.S. ProvisionalApplication No. 60/271,319, filed Feb. 23, 2001, the contents of whichare hereby incorporated by reference.

[0002] The invention disclosed herein was made with Government supportunder grant numbers NS 29832-09 from the National Institutes of Healthand 2POICA23767-22 from the National Cancer Institute. Accordingly, theU.S. Government has certain rights in this invention.

BACKGROUND OF THE INVENTION

[0003] Throughout this application, various publications are referencedin parentheses. Full citations for these references may be found at theend of the specification immediately preceding the claims. Thedisclosures of these publications in their entireties are herebyincorporated by reference into this application to more fully describethe state of the art to which this invention pertains.

[0004] All animals have specialized mechanisms to recognize and respondto chemosensory information in the environment. Olfactory neuronsrecognize volatile cues that afford the organism the ability to detectfood, predators and mates. In contrast, gustatory neurons sense solublechemical cues that elicit feeding behaviors. In insects, taste neuronsalso initiate innate sexual and reproductive responses. In Drosophila,for example, sweet compounds are recognized by chemosensory hairs on theproboscis and legs that activate proboscis extension and feeding(Dethier, 1976). Sexually dimorphic chemosensory bristles on the forelegof males recognize cues from receptive females that are thought toelicit the embrace of mating (Tompkins et al., 1983; Possidente andMurphey, 1989). Females have yet a third set of specialized bristles ontheir genitalia that may cause oviposition in response to nutrients(Rice, 1977; Taylor, 1989). In this manner, gravid females willpreferentially deposit their eggs on a rich environment that enhancessurvival of their offspring. These robust and innate gustatory responsesprovide the opportunity to understand how chemosensory information isrecognized in the periphery and ultimately translated into specificbehaviors.

[0005] Taste in Drosophila is mediated by sensory bristles that resideon the proboscis, legs, wing, and genitalia (Stocker, 1994; Singh,1997). Most chemosensory bristles are innervated by four bipolargustatory neurons and a single mechanoreceptor cell (Falk et al., 1976).The dendrites of gustatory neurons extend into the shaft of the bristleand are the site of taste recognition that translates the binding oftastants into alterations in membrane potential. The sensory axons fromthe proboscis project to the brain where they synapse on projectionneurons within the subesophageal ganglion (SOG), the first relay stationfor gustatory information in the fly brain (Stocker and Schorderet,1981; Nayak and Singh, 1983; Shanbhag and Singh, 1992; Rajashekhar andSingh, 1994). Sensory axons from taste neurons at other sites along thebody project locally to peripheral ganglia (Power, 1948). Drosophilalarvae, whose predominant activity is eating, sense their chemicalenvironment with gustatory neurons that reside in chemosensory organs onthe head and are also distributed along the body surface (Stocker, 1994)The pattern of projection of functionally distinct classes of tastecells and therefore the nature of the representation of gustatoryinformation in the Drosophila brain remains unknown.

[0006] The identification of the genes encoding taste receptors and theanalysis of the patterns of receptor expression may provide insight intothe logic of taste discrimination in the fly. In Drosophila, therecognition of odorants is thought to be accomplished by about 70seven-transmembrane domain proteins encoded by the Drosophila odorantreceptor (DOR) gene family (Clyne et al., 1999; Gao and Chess, 1999;Vosshall et al., 1999; Vosshall et al., 2000). Recently, a large familyof putative G protein-coupled receptors was identified by searching theDrosophila genome with an algorithm designed to detectseven-transmembrane domain proteins (Clyne et al., 2000). These geneswere suggested to encode gustatory receptors (GRs) because members ofthis gene family were detected in the proboscis by RT-PCR experiments.

[0007] The present application characterizes and extends the family ofputative G protein-coupled receptors originally identified by Clyne etal. (2000) and provides evidence that they encode both olfactory andgustatory receptors. In situ hybridization, along with transgeneexperiments, reveals that some receptors are expressed intopographically restricted sets of neurons in the proboscis, whereasother members are expressed in spatially fixed olfactory neurons in theantenna. Members of this gene family are also expressed in chemosensorybristles on the leg and in larval chemosensory organs. Finally, theprojections of different subsets of larval chemosensory neurons weretraced to the subesophageal ganglion and the antennal lobe. These dataprovide insight into the diversity of chemosensory recognition in theperiphery and afford an initial view of the representation of gustatoryinformation in the fly brain.

SUMMARY OF THE INVENTION

[0008] This invention provides an isolated nucleic acid encoding aninsect gustatory receptor protein, wherein the receptor proteincomprises seven transmembrane domains and a C-terminal domain, and theC-terminal domain comprises consecutive amino acids having the followingsequence:

[0009] -G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQID NO: 60),

[0010] where X is any amino acid, and / means or.

[0011] The invention provides an isolated nucleic acid encoding aninsect odorant receptor protein, wherein the receptor protein comprisesseven transmembrane domains and a C-terminal domain, and the C-terminaldomain comprises consecutive amino acids having the following sequence:

[0012] -G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQID NO: 60)

[0013] where X is any amino acid, and / means or.

[0014] The invention provides an isolated nucleic acid encoding aninsect gustatory receptor protein, wherein the nucleic acid moleculeencodes a protein selected from the group consisting of:

[0015] (a) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2B1 in SEQ ID NO: 1,

[0016] (b) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr8D1 in SEQ ID NO: 2,

[0017] (c) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr10B1 in SEQ ID NO:3,

[0018] (d) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr10B2 in SEQ ID NO:4,

[0019] (e) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr28A2 in SEQ ID NO.5,

[0020] (f) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr28A4 in SEQ ID NO:6,

[0021] (g) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr33C1 in SEQ ID NO:7,

[0022] (h) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr36B2 in SEQ ID NO:8,

[0023] (i) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr36B3 in SEQ ID NO:9,

[0024] (j) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr59C1 in SEQ ID NO:10,

[0025] (k) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr61D1 in SEQ ID NO:11,

[0026] (l) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr63F1 in SEQ ID NO:12,

[0027] (m) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr64A2 in SEQ ID NO:13,

[0028] (n) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for GR64A3 in SEQ ID NO:14,

[0029] (o) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr66C1 in SEQ ID NO:15,

[0030] (p) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr92D1 in SEQ ID NO:16,

[0031] (q) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr98A1 in SEQ ID NO:17,

[0032] (r) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr98A2 in SEQ ID NO:18,

[0033] (s) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.1 in SEQ ID NO:19,

[0034] (t) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.2 in SEQ ID NO:20,

[0035] (u) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.3 in SEQ ID NO:21,

[0036] (v) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.4 in SEQ ID NO:22,

[0037] (w) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.5 in SEQ ID NO:23,

[0038] (x) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr57B1 in SEQ ID NO:46,

[0039] (y) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr93F1 in SEQ ID NO:48,

[0040] (z) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr93F2 in SEQ ID NO:49,

[0041] (aa) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr93F3 in SEQ IDNO: 50,

[0042] (bb) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr93F4 in SEQ IDNO: 51,

[0043] (cc) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr94E1 in SEQ IDNO: 52,

[0044] (dd) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr93D1 in SEQ IDNO: 53,

[0045] (ee) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU1=Gr36B1 inSEQ ID NO: 55,

[0046] (ff) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU2=Gr28A3 inSEQ ID NO: 56,

[0047] (gg) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU3=Gr64A1 inSEQ ID NO: 57,

[0048] (hh) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU7=Gr5A1 inSEQ ID NO: 59, and

[0049] (ii) an insect gustatory receptor protein which shares from 7-50%amino acid identity with any one of the proteins of (a)-(hh), andcomprises seven transmembrane domains and a C-terminal domain, whereinthe C-terminal domain comprises consecutive amino acids having thefollowing sequence:

[0050] -G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQID NO: 60),

[0051] where X is any amino acid, and / means or.

[0052] The invention provides an isolated nucleic acid molecule encodingan insect odorant receptor protein, wherein the nucleic acid moleculeencodes a protein selected from the group consisting of:

[0053] (a) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2B1 in SEQ ID NO: 1,

[0054] (b) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr8D1 in SEQ ID NO: 2,

[0055] (c) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr10B1 in SEQ ID NO:3,

[0056] (d) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr10B2 in SEQ ID NO:4,

[0057] (e) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr28A2 in SEQ ID NO:5,

[0058] (f) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr28A4 in SEQ ID NO:6,

[0059] (g) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr33C1 in SEQ ID NO:7,

[0060] (h) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr36B2 in SEQ ID NO:8,

[0061] (i) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr36B3 in SEQ ID NO:9,

[0062] (j) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr59C1 in SEQ ID NO:10,

[0063] (k) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr61D1 in SEQ ID NO:11,

[0064] (1) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr63F1 in SEQ ID NO:12,

[0065] (m) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr64A2 in SEQ ID NO:13,

[0066] (n) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for GR64A3 in SEQ ID NO:14,

[0067] (o) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr66C1 in SEQ ID NO:15,

[0068] (p) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr92D1 in SEQ ID NO:16,

[0069] (q) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr98A1 in SEQ ID NO:17,

[0070] (r) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr98A2 in SEQ ID NO:18,

[0071] (s) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.1 in SEQ ID NO:19,

[0072] (t) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.2 in SEQ ID NO:20,

[0073] (u) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.3 in SEQ ID NO:21,

[0074] (v) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.4 in SEQ ID NO:22,

[0075] (w) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.5 in SEQ ID NO:23,

[0076] (x) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr57B1 in SEQ ID NO:46,

[0077] (y) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr93F1 in SEQ ID NO:48,

[0078] (z) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr93F2 in SEQ ID NO:49,

[0079] (aa) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr93F3 in SEQ IDNO: 50,

[0080] (bb) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr93F4 in SEQ IDNO: 51,

[0081] (cc) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr94E1 in SEQ IDNO: 52,

[0082] (dd) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr93D1 in SEQ IDNO: 53,

[0083] (ee) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU1=Gr36B1 inSEQ ID NO: 55,

[0084] (ff) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU2=Gr28A3 inSEQ ID NO: 56,

[0085] (gg) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU3=Gr64A1 inSEQ ID NO: 57,

[0086] (hh) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU7=Gr5A1 inSEQ ID NO: 59, and

[0087] (ii) an insect odorant receptor protein which shares from 7-50%amino acid identity with any one of the proteins of (a)-(hh), andcomprises seven transmembrane domains and a C-terminal domain, whereinthe C-terminal domain comprises consecutive amino acids having thefollowing sequence:

[0088] -G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQID NO: 60),

[0089] where X is any amino acid, and / means or.

[0090] The invention provides a nucleic acid molecule comprising atleast 12 nucleotides which specifically hybridizes with any of theisolated nucleic acid molecules described herein.

[0091] This invention provides a vector which comprises any of theisolated nucleic acid molecules described herein.

[0092] The invention provides a host vector system for production of apolypeptide having the biological activity of an insect gustatory orodorant receptor, which comprises any of the vectors described hereinand a suitable host.

[0093] The invention provides a method of producing a polypeptide havingthe biological activity of an insect gustatory or odorant receptor whichcomprising growing any of the host vector systems described herein underconditions permitting production of the polypeptide and recovering thepolypeptide so produced.

[0094] The invention provides a purified insect gustatory or odorantreceptor protein encoded by any of the isolated nucleic acid moleculesdescribed herein.

[0095] The invention provides an antibody which specifically binds to aninsect gustatory or odorant receptor protein encoded by any of theisolated nucleic acid molecules described herein. The invention providesan antibody which competitively inhibits the binding of any of theantibodies described herein capable of specifically binding to an insectgustatory or odorant receptor.

[0096] The invention provides a method of transforming a cell whichcomprises transfecting a host cell with any of the vectors describedherein.

[0097] The invention provides a transformed cell produced by any of themethods described herein.

[0098] The invention provides a method of identifying a compound whichspecifically binds to an insect gustatory or odorant receptor whichcomprises contacting any of the transformed cells described herein, or amembrane fraction from said cells, with the compound under conditionspermitting binding of the compound to the gustatory or odorant receptor,detecting the presence of any such compound specifically bound to thereceptor, and thereby identifying the compound as a compound whichspecifically binds to an insect gustatory or odorant receptor.

[0099] The invention provides a method of identifying a compound whichspecifically binds to an insect gustatory or odorant receptor whichcomprises contacting any of the purified insect gustatory or odorantreceptor proteins described herein with the compound under conditionspermitting binding of the compound to the purified gustatory or odorantreceptor protein, detecting the presence of any such compoundspecifically bound to the receptor, and thereby identifying the compoundas a compound which specifically binds to an insect gustatory or odorantreceptor.

[0100] The invention provides a method of identifying a compound whichactivates an insect gustatory or odorant receptor which comprisescontacting any of the transformed cells described herein, or a membranefraction from said cells, with the compound under conditions permittingactivation of the gustatory or odorant receptor, detecting activation ofthe receptor, and thereby identifying the compound as a compound whichactivates an insect gustatory or odorant receptor.

[0101] The invention provides a method of identifying a compound whichactivates an insect gustatory or odorant receptor which comprisescontacting any of the purified insect gustatory or odorant receptorproteins described herein with the compound under conditions permittingactivation of the gustatory or odorant receptor, detecting activation ofthe receptor, and thereby identify the compound as a compound whichactivates an insect gustatory or odorant receptor.

[0102] The invention provides a method of identifying a compound whichinhibits the activity of an insect gustatory or odorant receptor whichcomprises contacting any of the transformed cells described herein, or amembrane fraction from said cells, with the compound under conditionspermitting inhibition of the activity of the gustatory or odorantreceptor, detecting inhibition of the activity of the receptor, andthereby identifying the compound as a compound which inhibits theactivity of an insect gustatory or odorant receptor.

[0103] The invention provides a method of identifying a compound whichinhibits the activity of an insect gustatory or odorant receptor whichcomprises contacting any of the purified insect gustatory or odorantreceptor proteins described herein with the compound under conditionspermitting inhibition of the activity of the gustatory or odorantreceptor, detecting inhibition of the activity of the receptor, andthereby identifying the compound as a compound which inhibits theactivity of an insect gustatory or odorant receptor.

[0104] The invention provides a compound identified by any of themethods described herein.

[0105] The invention provides a method of combating ingestion of cropsby pest insects which comprises identifying a compound by any of themethods described herein and spraying the crops with the compound.

[0106] The invention provides a method of controlling a pest populationin an area which comprises identifying a compound any of the methodsdescribed herein and spraying the area with the compound.

[0107] The invention provides a composition which comprises a compoundidentified by any of the methods described herein and a carrier.

[0108] The invention provides a method of preparing a composition whichcomprises identifying a compound by any of the methods described herein,recovering the compound from the receptor protein, and admixing acarrier.

BRIEF DESCRIPTION OF THE FIGURES

[0109] FIGS. 1A-1B. The signature motif of GRs is present but divergedin members of the DOR gene family.

[0110] Sequence alignments of the complete DOR and GR gene familiesreveal a common amino acid motif in the putative seventh transmembranedomain of the carboxyl terminus of all GRs and 33 DORs. Alignments areshown for 23 GRs and 33 DORs (from top to bottom of figure, SEQ ID NO:61 through SEQ ID NO: 116, respectively). The average identity in theC-terminus is 29% for the GRs, 25% for the DORs, and 20% for the GRsplus DORs. Sequence relationships between the GR gene family and the DORgenes were analyzed with HMMs (Eddy, 1998), CLUSTAL alignments andneighbor joining trees (Saitou and Nei, 1987; Higgins and Sharp, 1988),and NxN BLASTP (Rubin et al., 2000) comparisons. The consensus alignmentand coloring of conserved residues was assigned in ClustalX.

[0111] FIGS. 2A-2B. Expression of GR genes in the proboscis and antenna

[0112] Digoxigenin-labeled antisense riboprobes derived from GRsequences hybridize to subsets of cells in adult chemosensory organs.(A) Six genes show specific hybridization to gustatory tissues. Gr47A1,Gr66C1, Gr32D1, Gr98A1, Gr28A3 and Gr33C1 are expressed in single cellswithin chemosensory sensilla of the proboscis labellum (data not shownfor Gr28A3 and Gr33C1). (B) Three genes, Gr63F1, Gr10B1, and Gr21D1, arespecifically detected in the medial aspect of the third antennalsegment, the adult olfactory organ. These expression patterns weremaintained in more than 50 heads for each riboprobe. Probes wereannealed to sagittal sections (15 um) of the adult fly head to assay forexpression in the proboscis and to frontal sections to examineexpression in the antenna.

[0113]FIG. 3. A spatial map of GR expression in the proboscis GRpromoter-Gal4 transgenes drive expression in subsets of cells in theproboscis. Flies containing GR promoter-Gal4 and UAS-lacZ transgeneswere examined for B-galactosidase activity staining on labial palp wholemounts. Each labial palp contains 31-36 chemosensory sensilla, arrangedin approximately four rows. In the diagram of a labial palp, differentrows of sensilla are depicted in different colors (adapted from Ray etal., 1993). Individual GRs show restricted expression in discretesubsets of chemosensilla. Gr47A1 is expressed in 9-11 sensillainnervating the most peripheral row of bristles, Gr32D1 is expressed in6 sensilla innervating an intermediate row of bristles, Gr22B1 isexpressed in only 3-4 sensilla innervating small bristles, and Gr66C1and Gr28A3 are expressed in 8-10 sensilla innervating small or mediumbristles. The spatial patterns for the different receptors are identicalin 2-5 independent transformant lines for each promoter construct, andare also fixed among over 20 different individuals within a line.

[0114] FIGS. 4A-4E. GRs are expressed in a variety of chemosensoryneurons

[0115] (A, B) Expression of GFP allows visualization of dendrites andaxons of neurons in the proboscis. GFP was detected in labial palp wholemounts of GR promoter-Gal4: UAS-GFP flies by direct fluorescencemicroscopy. Each transgene drives expression of GFP in a single bipolarneuron within a sensillum. Gr66C1 is expressed in 9 neurons (6-7 infocus) (A) and Gr22B1 is expressed in 3 neurons (B) innervatingdifferent rows of chemosensory bristles.

[0116] (C, D, E) GRs are expressed in chemosensory sensilla that resideon the internal mouthparts of the proboscis and on tarsal segments oflegs. In addition to expression in the proboscis labellum, Gr32D1,Gr66C1 and Gr28A3 are also detected in the cibarial organs of the mouth.(C) LacZ expression in a whole mount proboscis is illustrated for theGr66C1-Gal4: UAS-lacZ line. The arrow denotes the cibarial organ. (D)One transgenic line, Gr2B1-Gal4, drives expression exclusively in thelabral sense organ of the mouth, and not in the cibarial organs or inthe labellum of the proboscis. The arrow denotes the labral sense organ.(E) Gr32D1 is expressed in the proboscis labellum and in the cibarialorgans. In addition, Gr32D1-Gal4 drives expression of GFP in 2-3 neuronsin the fourth and fifth tarsal segments of all legs. Receptor expressionwas examined by B-galactosidase activity staining of GR promoter-Gal4:UAS-lacZ flies (C, D) or by fluorescent visualization of GRpromoter-Gal4: UAS-GFP flies (E).

[0117] FIGS. 5A-5G. GRs are expressed in larval chemosensory neurons

[0118] (A) The antenno-maxillary complex of larvae is a bilaterallysymmetric structure containing the dorsal organ mediating smell and theterminal organ involved in both taste and smell. Shown is the anteriorventral region of a larva viewed by differential interference contrast.On one half of the larval head, the sensilla of the terminal organ isoutlined with black dotted lines and the pore of the terminal organ isdenoted by an outlined arrow. The dome of the dorsal organ is denoted bya filled arrowhead.

[0119] (B-E) Gr32D1, Gr66C1, and Gr28A3 are expressed in the proboscislabellum in the adult (FIG. 3), and are expressed in a singlebilaterally symmetric neuron in the terminal organ of larvae (B, E, datanot shown). Gr2B1 is expressed in the labral sense organ of the adultproboscis, and is expressed in two neurons innervating the dorsal organ(filled arrow), one neuron innervating the terminal organ (outlinedarrow), and one neuron innervating the ventral pits in each of thethoracic segments in larvae (C). Gr21D1 is expressed in the adultantenna and in a single larval neuron innervating the terminal organ(D). The dome of the dorsal organ is autoflourescent.

[0120] (F, G) Different GRs are expressed in distinct chemosensoryneurons. In larvae bearing two GR promoter-Gal4 fusions and UAS-GFP, twoGFP positive cells per terminal organ are observed. The differentpromoter combinations illustrated are Gr21D1-Gal4 plus Gr66C1-Gal4 (F)and Gr32D1-Gal4 plus Gr66C1-Gal4 (G). The pseudotracheae of the larvalmouth shows autoflourescence.

[0121] FIGS. 6A-6H. Axonal Projections of Larval Chemosensory Neurons

[0122] Projections of neurons bearing different GRs are spatiallysegregated in the larval brain. In all panels, whole mount larval brainsfrom GR promoter-Gal4: UAS-nSyb-GFP flies were stained with anti-GFP tolabel axonal termini (green), mAb nc82 to label neuropil (red), andTOTO-3 to counterstain nuclei (blue). Each image represents a compositeof 1 um optical sections through the larval brain, encompassing theterminal projections. Projections extend 5-10 um in depth for B, C, D, Gand 10-20 um in depth for E, F, G.

[0123] (A) The larval brain is composed of the two dorsal brainhemispheres (BH) and the ventral hindbrain (HB). The subesophagealganglion (SOG) resides in the hindbrain, at the juncture of thehindbrain with the brain hemispheres. The antennal lobe (AL) is a smallneuropil on the anterior edge of the brain hemisphere (denoted with anarrow in panel E, G).

[0124] (B-D) GR-bearing neurons project to discrete locations in thelarval brain. Gr32D1 is expressed in the proboscis in the adult and inone neuron in the terminal organ in larvae. In Gr32D1-Gal4:UAS-nSyb-GFPlarval brains, a single terminal arborization is observed in the SOG (C). A similar pattern is observed for neurons expressing Gr66C1, a geneexpressed in the adult proboscis and in a single neuron in the terminalorgan and two in the mouth of larvae (B, D). Panels D is a highermagnification (3×) of Panel D.

[0125] (E) Projections of gustatory neurons from different body regionsare spatially segregated in the fly brain. Gr2B1 is expressed in twoneurons innervating the dorsal organ, one neuron innervating theterminal organ, and one neuron innervating the ventral pits. Axons fromventral pit neurons enter the hindbrain via thoracic nerves andterminate in the antennal lobe (arrows), in a location that is distinctfrom the termini of other Gr2B1-bearing neurons.

[0126] (F) Segregation is less apparent in the terminal projections oftwo different taste receptors. Larvae that contain Gr66C1-Gal4 andGr32D1-Gal4 along with UAS-nSyb-GFP reveal two partially overlappingprojection patterns.

[0127] (G, H) Distinct projection patterns are observed for the twodifferent chemosensory modalities, taste and smell. Gr21D1 is expressedin the adult antenna and in a single neuron in the terminal organ oflarvae. Gr21D1 axons enter the antennal lobe (arrows) (G). In larvaethat contain Gr21D1-Gal4 and Gr66C1-Gal4 along with UAS-nSyb-GFP, twodiscrete termini are apparent, one entering the SOG, and a secondentering the antennal lobe (H).

[0128] FIGS. 7A-7C. A subset of GRs encode olfactory receptorsGR-bearing neurons in the antenna project to discrete glomeruli in theantennal lobe. Adult transgenic flies in which Gr21D1 promoter-Gal4drives expression of UAS-lacZ

[0129] (A) or UAS-GFP (B) show specific labelling in subsets of cells inthe medial aspect of the antenna. This expression pattern resembles thatdetermined for the endogenous gene. LacZ expression was detected in 15um frontal sections of the antenna (A); GFP expression was examined inwhole antennae (B).

[0130] (C) Gr21D1-bearing neurons project to a single bilaterallysymmetric glomerulus on the ventral-most region of the antennal lobe.Whole mount brains of Gr21D1-Gal4: UAS-nSyb-GFP flies were examined byfluorescent immunohistochemistry, with anti-GFP to visualize axonaltermini of Gr21D1-bearing neurons (green), mAb nc82 to label brainneuropil (red), and TOTO-3 to counterstain nuclei (blue). Gr21D1-bearingneurons send projections to the V glomerus in the antennal lobe (Stockeret al., 1990; Laissue et al., 1999) and do not project to thesubesophageal ganglion (located in the bottom part of C).

DETAILED DESCRIPTION OF THE INVENTION

[0131] Throughout this application, the following standard abbreviationsare used to indicate specific amino acids: 3-character 1-characterabbreviation Amino Acid abbreviation Ala Alanine A Arg Arginine R AsnAsparagine N Asp Aspartic Acid D Cys Cysteine C Gln Glutamine Q GluGlutamic Acid E Gly Glycine G His Histidine H Ile Isoleucine I LeuLeucine L Lys Lysine K Met Methionine M Phe Phenylalanine F Pro ProlineP Ser Serine S Thr Threonine T Trp Tryptophane W Tyr Tyrosine Y ValValine V Asx Asparagine/ B Aspartic Acid Glx Glutamine/ Z Glutamic Acid*** (End) * Xxx Unidentified, any, or X as specified.

[0132] Throughout this application, the following standard abbreviationsare used to indicate specific nucleotides:

[0133] C=cytosine A=adenosine

[0134] T=thymidine G=guanosine.

[0135] This invention provides a family of isolated nucleic acidmolecules encoding insect gustatory and odorant receptors. In oneembodiment, the receptor is a gustatory receptor. In one embodiment, thereceptor is an odorant receptor.

[0136] The family of receptors comprises:

[0137] Newly identified receptors disclosed herein comprise: Gr2B1MDTLRALEPLHRACQVCNLWPWRLAPPPDSEGILLRRSRWLELYGWTVLIAATSFTV (SEQ ID NO:1)YGLFQESSVEEKQDSESTISSIGHTVDFIQLVGMRVAHLAALLEALWQRQAQRGFFAELGEIDRLLSKALRVDVEAMRINMRRQTSRPAVWILWGYAVSQLLILGAKLLSRGDRFPIYWISYLLPLLVCGLRYFQIFNATQLVRQRLDVLLVALQQLQLHQKGPAVDTVLEEQEDLEEAAMDRLIAVRLVYQRVWALVALLNRCYGLSMLMQVGNDFLAITSNCYWMFLNFRQSAASPFDILQIVASGVWSAPHLGNVLVLSLLCDRTAQCASRLALCLHQVSVDLRNESHNALITQFSLQLLHQRLHFSAAGFFNVDCTLLYTIVGATTTYLIILIQFHMS ESTIGSDSNGQGr8D1 MSGHLGRVLQFHLRLYQVLGFHGLPLPGDGNPARTRRRLMAWSLFLLISLSALVLAC (SEQ IDNO:2) LFSGEEFLYRGDMFGCANDALKYVFAELGVLAIYLETLSSQRHLANFWWLHFKLGGQKTGLVSLRSEFQQFCRYLIFLYAMMAAEVAIHLGLWQFQALTQHMLLFWSTYEPLVWLTYLRNLQFVLHLELLREQLTGLEREMGLLAEYSRFASETGRSFPGFESFLRRRLVQKQRIYSHVYDMLKCFQGAFNFSILAVLLTINIRIAVDCYFMYYSIYNNVINNDYYLIVPALLEIPAFIYASQSCMVVVPRIAHQLHNIVTDSGCCSCPDLSLQIQNFSLQLLHQPIRIDCLGLTILDCSLLTRMACSVGTYMIYSIQFIPKFSNTYM Gr10B1MQRTHLEFEFKNAPQEPKRPFEFFMYFKFCLINLMMMIQVCGIFAQYGEVGKGSVSQ (SEQ ID NO:3)VRVHFAIYAFVLWNYTENMADYCYFINGSVLKYYRQFNLQLGSLRDEMDGLRPGGMLLHHCCELSDRLEELRRRCREIHDLQRESFRMHQFQLIGLMLSTLINNLTNFYTLFHMLAKQSLEEVSYPVVVGSVYATGFYIDTYIVALINEHIKLELEAVALTMRRFAEPREMDERLTREVRNKIFSFLATTLEIMIQIWLSFPANFDDVTPYRKCENRPKNLFFKIRQKVIGIVSSGKLKLLVSLRFFIIDNRLILNLHKYLAIKLNFLNLIQIEHLSLELLNYQPPMLCGLLHLDRRLVYLIAVTAFSYFITLVQFDLYLRKKS Gr10B2MRVGKLCRLALRFWMGLILVLGFSSHYYNPTRRRLVYSRILQTYDWLLMVINLGAFY (SEQ ID NO:4)LYYRYAMTYFLEGMFRRQGFVNQVSTCNVFQQLLMAVTGTWLHFLFERHVCQTYNELSRILKHDLKLKEHSRFYCLAFLAKVYNFFHNFNFALSAIMHWGLRPFNVWDLLANLYFVYNSLARDAILVAYVLLLLNLSEALRLNGQQEHDTYSDLMKQLRRRERLLRIGRRVHRMFAWLVAIALIYLVFFNTATIYLGYTMFIQKHDALGLRGRGLKMLLTVVSFLVILWDVVLLQVICEKLLAEENKICDCPEDVASSRTTYRQWEMSALRRAITRSSPENNVLGMFRMDMRCAFALISCSLSYGIIIIQIGYIPG Gr28A2MAFKLWERFSQADNVFQALRPLTFISLLGLAPFRLNLNPRKEVQTSKFSFFAGIVHF (SEQ ID NO:5)LFFVLCFGISVKEGDSIIGYFFQTNITRFSDGTLRLTGILAMSTIFGFAMFKRQRLVSIIQNNIVVDEIFVRLGMKLDYRRILLSSFLISLGMLLFNVIYLCVSYSLLVSATISPSFVTFTTFALPHINISLMVFKFLCTTDLARSRFSMLNEILQDILDAHIEQLSALELSPMHSVVNHRRYSHRLRNLISTPMKRYSVTSVIRLNPEYAIKQVSNIHNLLCDICQTIEEYFTYPLLGIIAISFLFILFDDFYILEAILNPKRLDVFEADEFFAFFLMQLIWYIVIIVLIVEGSSRTILHSSYTAAIVHKILNITDDPELRDRLFRLSLQLSHRKVLFTAAGLFRLDRTLIFTVN FLQITGAATCYLIILIQF Gr28A4MIRCGLDIFRGCRGRFRYWLSARDCYDSISLMVAIAFALGITPFLVRRNALGENSLEQ (SEQ ID NO:6)SWYGFLNAIFRWLLLAYCYSYINLRNESLIGYFMRNHVSQISTRVHDVGGIIAAVFTFILPLLLRKYFLKSVKNMVQVDTQLERLRSPVNFNTVVGQVVLVILAVVLLDTVLLTTGLVCLAKMEVYASWQLTFIFVYELLAISITICMFCLMTRTVQRRITCLHKFDFATMSALRRVRKYFISSQVYEALRPLFFLTFLYGLTPFHVVRRKMGESYLKMSCFGVFNIFIYICLCGFCYISSLRQGESIVGYFFRTEISTIGDRLQIFNGLIAGAVIYTSAILKRCKLLGTLTILHSLDTNFSNIGVRVKYSRIFRYSLLVLIFKLLILGVYFVGVFRLLVSLDVTPSF CVCMTFFLQGr33C1 MKRKAVEVIGLIPLNRQQSETNFILDYAMMCIVPIFYVACYLLINLSHIIGLCLLDSC (SEQID NO:7) NSVCKLSSIHLFMHLGAFLYLTITLLSLYRRKEFFQQFDARLNDIDAVIQKCQRVAEMDKVKVTAVKHSVAYHFTWLFLFCVFTFALYYDVRSLYLTFGNLAFIPFMVSSFPYLAGSIIQGEFIYHVSVISQRFEQINMLLEKINQEARHRHAPLTVFDIESEGKKERKTVTPITVMDGRTTTGFGNENKFAGEMKRQEGQQKNDDDDLDTSNDEDEDDFDYDNATIAENTGNTSEANLPDLFKLHDKILALSVITNGEFGPQCVPYMAACFVVSIFGIFLETKVNFIVGGKSRLLDYMTYLYVIWSFTTMMVAYIVLRLCCNANNHSKQSAMIVHEIMQKKPAFMLSNDLFYNKMKSFTLQFLHWEGFFQFNGVGLFALDYTFIFSTVSAATSYLIVLLQFDMTAI LRNEGLMSGr36B2 MVDWVVLLLKAVHIYCYLIGLSNFEFDCRTGRVFKSRRCTIYAFMANIFILITIIYNF (SEQID NO:8) TAHGDTNLLFQSANKLHEYVIIIMSGLKIVALITVLNRWLQRGQMMQLVKDVIRLYMINPQLKSMIRWGILLKAFISFAIELLQVTLSVDALDRQGTAEMMGLLVKLCVSFIMNLAISQHFLVILLIRAQYRIMNAKLRMVIEESRRLSFLQLRNGAFMTRCCYLSDQLEDIGEVQSQLQSMVGQLDEVFGMQGLMAYSEYYLSIVGTSYMSYSIYKYGPHNLKLSAKTSIIVCILTTLFYLDALVNCNNMLRVLDHHKDFLGLLEERTVFASSLDIRLEESVSFESLQLQLARNPLKINVMGMFPITRGSTAANCASVIVNSIFLIQFDME Gr36B3MDLESFLLGAVYYYGLFIGLSNFEFDWNTGRVFTKKWSTLYAIALDSCIFALYIYHWT (SEQ ID NO:9)GNTNIVNAIFGRANMLHEYVVAILTGLRIVTGLFTLILRWYQRCKMMDLASKVVRMYVARPQVRRMSRWGILTKFIFGSITDGLQMAMVLSAMGSRVDSQFYLGLGLQYWMFVILNMAMMQQHMIMLFVRTQFQLINTELRQVIDEAKDLLLSPRHQGVFMTKCCSLADQIENIARIQSQLQTIMNQMEEVFGIQGAMTYGGYYLSSVGTCYLAYSILKHGYENLSMTLSTVILAYSWCFFYYLDGMLNLSVMLHVQDDYWEMLQILGKRTIFVGLDVRLEEAVST Gr59C1MIKLYFRYSLAIGITSQQFSNRKFFSTLFSRTYALIANIVTLIMLPIVMWQVQLVFQQK (SEQ IDNO:10) KTFPKLILITNNVREAVSFLVILYTVLSRGFRDTAFKEMQPLLLTLFREEKRCGFKGIGGVRRSLRILLFVKFFTLSWLCVTDVLFLLYSTDALIWVNVLRFFFKCNTNNILEMVPMGYFLALWHIARGFDCVNRRLDQIVKSKSTRKHRELQHLWLLUACLTKTALNINKIYAPQMLASRFDNFVNGVIQAYWGAVFTFDLSTPFFWVVYGSVQYHVRCLDYYLIDNMCDVAVEYHDSAKHSWSEVRWTKEVSAFGSILLYICMLMQLLSFQISSYVIYANSTKLQLWSCGLFQANRSMWFAMISSVLYYILVLLQFHLVMRK* Gr61D1MSRTSDDIRKHLKVRRQKQRAILAMRWRCAQGGLEFEQLDTFYGAIRPYLCVAQFFGIM (SEQ IDNO:11) PLSNIRSRDPQDVKFKVRSIGLAVTGLFLLLGGMKTLVGANILFTEGLNAKNIVGLVFLIVGMVNWLNFVGFARSWSHIMLPWSSVDILMLFPPYKRGKRSLRSKVNVLALSVVVLAVGDHMLYYASGYCSYSMHILQCHTNHSRITFGLYLEKEFSDIMFIMPFNIFSMCYGFWLNGAFTFLWNFMDIFIVMTSIGLAQRFQQFAARVGALEGRHVPEALWYDIRRDHIRLCELASLVEASMSNIVFVSCANNVYVICNQALAIFTKLRHPINYVYFWYSLIFLLARTSLVFMTASKIHDASLLPLRSLYLVPSDGWTQEVQRFADQLTSEFVGLSGYRLPCLTRKSLFGMLATLVTYELMLLQIDAKSHKGLRCA Gr63F1MRPSGEKVVKGHGQGNSGHSLSGMANYYRRKKGDAVFLNAKPLNSANAQAYLYGVRKYS (SEQ IDNO:12) IGLAERLDADYEAPPLDRKKSSDSTASNNPEFKPSVFYRNIDPINWFLRIIGVLPIVRHGPARAKFEMNSASFIYSVVFFVLLACYVGYVANNRIHIVRSLSGPFEEAVIAYLFLVNILPIMIIPILWYEARKIAKLFNDWDDFEVLYYQISGHSLPLKLRQKAVYIAIVLPILSVLSVVITHVTMSDLNINQVVPYCILDNLTAMLGAWWFLICEAMSITAHLLAERFQKALKHIGPAAMVADYRVLWLRLSKLTRDTGNALCYTFVFMSLYLFFIITLSIYGLMSQLSEGFGIKDIGLTITALWNIGLLFYICDEAHYASVNVRTNFQKKLLMVELNWMNSDAQTEINMFLRATEMNPSTINCGGFFDVNRTLFKGLLTTMVTYLVVLLQFQISIPTDKGDSEGANNITVVDFVMDSLDNDMSLMGASTLSTTTVGTTLPPPIMKLKGRKG Gr64A2MPVRKVSSKFAEDLTFTWFSVRSYYALVTILFFGVSSGYMVAFVTSVSFNFDSVETLVF (SEQ IDNO:13) YLSIFLISLSFFQLARKWPEIAQSWQLVEAKLPPLKLPKERRSLAQHINMITIVATTCSLVEHIMSMLSMGYYVNSCPRWPDRPIDSFLYLSFSSVFYFVDYTRFLGIVGKVVNVLSTFAWNFNDIFVMAVSVALAARFRQLNDYMMREARLPTTVDYWMQCRINFRNLCKLCEEVDDAISTITLLCFSNNLYFICGKILKSMQAKPSIWHALYFWFSLVYLLGRTLILSLYSSSINDESKRPLVIFRLVPREYWCDELKRFSEEVQMDNVALTGMKFFRLTRGVVISVAGTIVTYELILLQFNGEEK Gr64A3MELSRSDKEAFLSDGSFHQAVGRVLLVAEFFAMMPVKGVTGKHPSDLSFSWRNIRTCF (SEQ IDNO:14) SLLFIASSLANFGLSLFKVLNNPISFNSIKPIIFRGSVLLVLIVALNLARQWPQLMMYWHTVEKDLPQYKTQLTKWKMGHTISMVMLLGMMLSFAEHILSMVSAINYASFCNRTADPIQNYFLRTNDEIFFVTSYSTTLALWGKFQNVFSTFIWNYMDLFVMIVSIGLASKFRQLNDDLRNFKGMNMAPSYWSERRIQYRNTCILCDKMDDAISLITMVSFSNNLYFICVQLLRSLNTMPSVAHAVYFYFSLIFLIGRTLAVSLYSSSVHDESRLTLRYLRCVPKESWCPEVKRFTEEVISDEVALTGMKFFHLTRKLVLSVAGTIVTYELVLIQFHEDNDLWDCDQSYYS Gr66C1MDNMAQAEDAVQPLLQQFQQLFFISKIAGILPQDLEKFRSRNLLEKSRNGMIYMLSTLI (SEQ IDNO:15) LYVVLYNILIYSFGEEDRSLKASQSTLTFVIGLFLTYIGLIMMVSDQLTALRNQGRIGELYERIRLVDERLYKEGCVMDNSTIGRRIRIMLIMTVIFELSILVSTYVKLVDYSQWMSLLWIVSAIPTFINTLDKIWFAVSLYALKERFEAINATLEELVDTHEKHKLWLRGNQEVPPPLDSSQPPQYDSNLEYLYKELGAIDAASRKPPPPPLATNMVHESELGNAAKVEEKLNNLCQVHDEICEIGKALNELWSYPILSLMAYGFLIFTAQLYFLYCATQYQSIPSLFRSAKNPFITVIVLSYTSGKCVYLIYLSWKTSQASKRTGISLHKCGVVADDNLLYEIVNHLSLKLLNHSVDFSACGFFTLDMETLYGVSGGITSYLIILIQFNLAAQQAKEAIQTFNSLNDTAGLVGAATDMDNISSTLRDFVTTTMTPAV Gr92D1MFEFLHQMSAPKLSTSILRYIFRYAQFIGVIFFCLHTRKDDKTVFIRNWLKWLNVTHRI (SEQ IDNO:16) ITFTRFFWVYIASISIKTNRVLQVLHGMRLVLSIPNVAVILCYHIFRGPEIIDLINQFLRLFRQVSDLFKTKTPGFGGRRELILILLNLISFAHEQTYLWFTIRKGFSWRFLIDWWCDFYLVSATNIFIHINSIGYLSLGVLYSELNKYVYTNLRIQLQKLNTSGSKQKIRRVQNRLEKCISLYREIYHTSIMFHKLFVPLLFLALIYKVLLIALIGFNVAVEFYLNSFIFWILLGKHVLDLFLVTVSVEGAVNQFLNIGMQFGNVGDLSKFQTTVSQFIFIDFIPI Gr98A1MVAQKSRLLARAFPYLDIFSVFALTPPPQSFGHTPHRRLRWYLMTGYVFYATAILATVF (SEQ IDNO:17) IVSYFNIIAIDEEVLEYNVSDFTRVMGNIQKSLYSIMAIANHLNMLINYRRLGGIYKDIADLEMDMDEASQCFGGQRQRFSFRFRMALCVGVWMILMVGSMPRLTMTAMGPFVSTLLKILTEFVMIMQQLKSLEYCVFVLIIYELVLRLRRTLSQLQEEFQDCEQQDMLQALCVALKRNQLLLGRIWRLEGDVGSYPTPTMLLLFLYNGLTILHMVNWAYINKFLYDSCCQYGPEYCLFVLLVYELILRTRHVLEQLKDDLEDFDCGARIQELCVTLKQNQLLIGRIWRLVDEIGAYFRWSMTLLFLYNGLTILHVVNWAIIRSIDPNDCCQLMSFHFSLNMEANRSRLLAAARPYIQIYSIFGLTPPIQFFTRTLHKRRRGIVILGYACYLISISLMVIYECYANIVALQKDIHKFHAEDSSKVMGNTQKVLVVAMFVWNQLNILLNFRRLARIYDDIADLEIDLNNASSGFVGQRHWWRFRFRLALSVGLWIVLLVGLTPRFTLVALGPYLHWTNKVLTEIILIMLQLKCTEYCVFVLLTYELILRGRHILQQISVELEGNQSRDSVQELCVALKRNQLLAGRIWGLVNEVSLYFTLSLTLLFLYNELTILQIVWNWALIKSVNPNECCQYTEDYLILKMGLREYSLQMEHLKLIFTCGGLFDINLKFFGGVKLKL Gr98A2MEAKRSRLLTTARPYLQVLSLFGLTPPAEFFTRTLRKRRRFCWMAGYSLYLIAILLMVF (SEQ IDNO:18) YEFHANIVSLHLEIYKFHVEDFSKVMGRIQKFLTVAIATCNQLNILLNYGRLGLIYDEIANLDLGIDKSSKNFCGKSHWWSFRLRLTLSIGLWMVIIIGVIPRLTLGPAGPFFHWVNQVLTQIILIMLQLKGPEYCLFVLLVYELILRTRHVLEQLKDDLEDFDCGARIQELCVTLKQNQLLIGRIWRLVDEIGAYFRWSMTLLFLYNGLTILHVVNWAIIRSIDPNDCCQLSEE Gr2940.1MFRPSGSGYRQKWTGLTLKGALYGSWILGVPPFAYDSWTRTLRRSKWLIAYGFVLNAAF (SEQ IDNO:19) ILLVVTNDTESETPLRMEVFHRNALAEQINGIHDIQSLSMVSIMLLRSFWKSGDIERTLNELEDLQHRYFRNYSLEECISFDRFVLYKGFSVVLELVSMLVLELGMSPNYSAQFFIGLGSLCLMLLAVLLGASHFHLAVVFVYRYVWIVNRELLKLVNKMAIGETVESERMDLLLYLYHRLLDLGQRLASIYDYQMVMVMVSFLIANVLGIYFFIIYSISLNKSLDFKILVFVQALVINMLDFWLNVEICELAERTGRQTSTILKLFNDIENIDEKLERSVSFTSQHYCETDFALFCSHRRLRFHIICGLFYVNYEMGFRMAITSFLYLLFLIQFDYWNL Gr2940.2MVKQAEDREHGIMLDVFQRNALLYQISSLMGVVGVVSICTVHLRTLWRSKHLEEIYNGL (SEQ IDNO:20) MLLEAKYFCSNAVECPAFDGYVIQKGVVIVVGLLAPWMVHFGMPDSKLPVLNVLVVSMVKLGTLLLALHYHLGVVIIYRFVWLINRELLSLVCSLRGNHKGSSSRVRFLLKLYNKLVNLYSKLADCYDCQTVLMMAIFLAANIIVCFYMIVYRISLSKMSFFVMLIMFPLAIANNFMDFWLSMKVCDLLQKTGRQTSMILKLFNDIENMDKDLEISISDFALYCSHRRFKFLHCGLFHVNREMGFKMFVASVLYLLYLVQF Gr2940.3MFASRSDLQSRLCWIILKATLYSSWFLGVFPYRFDSRNGQLKRSRFLLFYGLILNFFLL (SEQ IDNO:21) LKMVCSGGQKLGIPEAFARNSVLENTHYTTGMLAVFSCVVIHFLNFWGSTRVQDLANELLVLEYQQFASLNETKCPKFNSFVIQKWLSVIGLLLSYLSIAYGLPGNNFSVEMVLINSLVQFSFNCNIMHYYIGVLLIYRYLWLINGQLLEMVTNLKLDCSVDSSRIRKYLSLYRRLLELKGYMVATYEYHMTLVLTTGLASNFLAIYSWIVLDISMNINFIYLLIFPLFLLVNVWNLWLSIAASDLAENAGKSTQTVLKLFADLEVKDIELERSVSVNSNRYKQVNEFALLCGHCQFNFHVCGLFTINYKMGFQMIITSFLYLIYMIQFD Gr2940.4MINVVIGIINVLSALIVHFMNFWGSRKVGEICNELLILEYQDFEGLNGRNCPNFNCFV (SEQ IDNO:22) IQKCLTILGQLLSFFTLNFALPGLEFHICLVLLSCLMEFSLNLNIMHYHVGVLLIYRYVWLINEQLKDLVSQLKLNPETDFSRIHQFLSLYKRLLELNRKLVIAYEYQMTLFIIAQLSGNIVVIYFLIVYGLSMRTYSIFLVAFPNSLLINIWDFWLCIAACDLTEKAGDETAIILKIFSDLEHRDDKLEKFRFQLCGLFSMNCRMGFKMIITTFLYLVYLVQFDYMNL* Gr2940.5MSQPKRIHRICKGLARFTIRATLYGSWVLGLFPFTFDSRKRRLNRSKWLLAYGLVLNL (SEQ IDNO:23) TLLVLSMLPSTDDHNSVKVEVFQRNPLVKQVEELVEVISLITTLVTHLRTFSRSSELVEILNELLVLDKNHFSKLMLSECHTFNRYVIEKGLVIILEIGSSLVLYFGIPNSKIVVYEAVCIYIVQLEVLMVVMHFHLAVIYIYRYLWIINGQLLDMASRLRRGDSVDPDRIQLLLWLYSRLLDLNHRLTAIYDIQVTLFMATLFSVNIIVGHVLVICWINITRFSLLVIFLLFPQALIINFWDLWQGIAFCDLAESTGKKTSMILKLFNDMENMDQETERRVSEYMFQNLMYFKYFKHPLIFVAEFTLFCSHRRLKVCHLGLLDINYEMGFRMIITNILYVVFLVQFD YMNLPreviously reported Gustatory Receptors which are family members: a)Full-length clones Gr21D1MGVMPIHRNPPEKNLPRTGYSWGSKQVMWAIFIYSCQTTIVVLVLRERVKKFVTSPDK (SEQ IDNO:24) RFDEAIYNVIFISLLFTNFLLPVASWRHGPQVAIFKNMWTNYQYKFFKTTGSPIVFPNLYPLTWSLCVFSWLLSIAINLSQYFLQPDFRLWYTFAYYPIIAMLNCFCSLWYINCNAFGTASRALSDALQTTIRGEKPAQKLTEYRHLWVDLSHMMQQLGRAYSNMYGMYCLVIFFTTITATYGSISEIIDHGATYKEVGLFVIVFYCMGLLYIICNEAHYASRKVGLDFQTKLLNINLTAVDAATQKEVEMLLVAINKNPPIMNLDGYANINRELITTNISFMATYLVVLLQFKITEQRRIGQQQA Gr22B1MFQPRRGFSCHLAWFMLQTTLYASWLLGLFPFTFDSRRKQLKRSRWLLLYGFVLHSL (SEQ ID NO:25)AMCLAMSSHLASKQRRKYNAFERNPLLEKIYMQFQVTTFFTISVLLLMNVWKSNTVRKIANELLTLEGQVKDLLTLKNCPNFNCFVIKKHVAAIGQFVISIYFCLCQENSYPKILKILCCLPSVGLQLIIMHFHTEIILVYRYVWLVNETLEDSHHLSSSRIHALASLYDRLLKLSELVVACNDLQLILMLIIYLIGNTVQIFFLIVLGVSMNKRYIYLVASPQLIINFWDFWLNIVVCDLAGKCGDQTSKVLKLFTDLEHDDEELERSLNEFAWLCTHRKFRFQLCGLFSINHNMGFQMIITSFLYLVYLLQFDFMNLC Gr23A1aMKTLECLTRRFLEVIFSVLALVPLPPISQLGWLFLSLAIRCCWIVYFIYLLDVAISF (SEQ ID NO:26)SWVAIENVGNAVGTMLFVGNSVLGFALLLESVLKQKTHSQLEDLRVQTELQLQRLGMFGRSRHAAYLLPLIGVQFTCDLVRLATNFGETVSPVFCISLPLMWLLRYRYVQLVQHVMDLNQRSIHLRRSLLSMASGNDLWQPYGVQECLQLQTLRTTYERIFECYETFSDCYGWGMLGLHLLTSFQFVTNAYWMIMGIYDGGNVRSLIFNGATGIDFGTPIATLFWHGDSGAENGRQIGCLISKLVKPQGSKLYNDLVSEFSLQTLHQRFVVTAKDFFSLNLHLLSSMFAAVVTYLVILIQFMFAERSSTRGSG Gr23A1bMFPPTRVQASSRVVLKIFHFILVAFSLRSRRLSRLVLWLQFLGWLTWFISMWTQSVIY (SEQ IDNO:27) AQTIDCTLDCSLRHILTFFQTVSHAFIVVTSFLDGFRIKQDQLDEPIAFEDSDPWLAFTVLAMLVPTLGVEYLVCSNAPEYAFRIRIYHLKTLPSFLALQVQIISFILEVMKVNIRVRQTKLQLLILARELSCRWPQRKQKPQFSDQQAHRVKDLKRRYNDLHYLFVRINGYFGGSLLTIIIVHFAIFVSNSYWLFVDIRTRPWRIYAILLNLGFIFNVALQMAAACWHCQQSYNLGRQIGCLISKLVKPQGSKLYNDLVSEFSLQTLHQRFVVTAKDFFSLNLHLLSSMFAAVVTYLVILIQFMFAERSSTRGSG Gr32D1MPIYEQVSDYEVGPPTKTNEFYSFFVRGVVHALTIFNVYSLFTPISAQLFFSYRETDN (SEQ IDNO:28) VNQWIELLLCILTYTLTVFVCAHNTTSMLRIMNEILQLDEEVRRQFGANLSQNFGFLVKFLVGITACQAYIIVLKIYAVQGEITPTSYILLAFYGIQNGLTATYIVFASALLRIVYIRFHFINQLLNGYTYGQQHRRKEGGARARRQRGDVNPNVNPALMEHFPEDSLFIYRMHNKLLRIYKGINDCCNLILVSFLGYSFYTVTTNCYNLFVQITGKGMVSPNILQWCFAWLCLHVSLLALLSRSCGLTTTEVSNYIGDKISIFMSVFISRPMPHPKFLQGCMPSRRSIRISGFHYQIDKFLTKSIKQEVQFTAYGFFAIDNSTLFKIFSAVTTYLVILIQFKQLEDS KVEDPVPEQTGr39D1 MLYSFHPYLKYFALLGLVPWSESCAQSKFVQKVYSAILIILNAVHFGISIYFPQSAE (SEQ IDNO:29) LFLSLMVNVIVFVARIVCVTVIILQVMVHYDDYFRFCREMKYLGLRLQCELKIHVGRLKWQSYAKILALGIGFLVTVLPSIYVALSGSLLYFWSSLLSILIIRMQFVLVLLNVELLGHHVSLLGIRLQNVLECHLMGANCTLDGNANRLCSLEFLLALKQSHMQLHYLFTHFNDLFGWSILGTYVVLFSDSTVNIYWTQQVLVEVYEYKYLYATFSVFVPSFFNILVFCRCGEFCQRQSVLIGSYLRNLSCHPSIGRETSYKDLLMEFILQVEQNVLAINAEGFMSTDNSLLMSILAAKVTYLIVLMQFSSV Gr39D2aMGTRNRKLLFFLHYQRYLGLTNLDFSKSLHIYWLHGTWSSTAIQIVVVGVFMAALLG (SEQ ID NO:30)ALAESLYYMETKSQTGNTFDNAVILTTSVTQLLANLWLRSQQKSQVNLLQRLSQVVELLQFEPYAVPQFRWLYRIWLLVCLIYGAMVTHFGINWLTTMQISRVLTLIGFVYRCVLANFQFTCYTGMVVILKKLLQVQVKQLEHLVSTTTISMAGVAGCLRTHDEILLLGQRELIAVYGGVILFLFIYQVMQCTLIFYISNLEGFHSSNDLVLIFCWLAPMLFYLILPLVVNDIHNQANKTAKMLTKVPRTGTGLDRMIEKFLLKNLRQKPILTAYGFFALDKSTLFKLFTAIFTYMVILVQFKEMENSTKSINKF Gr39D2bMDFQPGELCAYYRLCRYLGIFCIDYNPTKKKFRLRRSVLCYIVHFALQAYLVGCISV (SEQ ID NO:31)MVTYWRRCFKSELTTTGNHFDRLVMVIALGILVVQNAWLIWLQAPHLRIVRQIEFYRRNHLANVRLLLPKRLLWLIIATNVVYMANFIKTCIFEWLTDASRLFVITSLGFPLRYLVTSFTMGTYFCMVHIVRLVLDWNQSQINAIIDESADLKMTSPNRLRLRVCLEMHDRLMLLCNDEISLVYGFIAWLSWMFASLDVTGVIYLTMVIQTKKSIVLKLITNVVWLSPTFMTCAASFMSNRVTIQANKTAKMLTKVPRTGTGLDRMIEKFLLKNLRQKPILTAYGFFALDKSTLFKLFTAIFTYMVILVQFKEMENSTKSINKF Gr39D2cMKRNAFEELRVQLRTLKWLGVLRFTIDFNKCLVRENASEERSAWLYLIGVVGITCSL (SEQ ID NO:32)IVYSTYFPSHFIMGKHNTTGNCYALINIRSCSIVTMLIYTQLYIQRFRFVALLQSILRFNQISGSHREEGRFAFYYYTHLSLLIICMLNYAYGYWTAGVRLTTIPIYLLQYGFSYLFLGQVVVLFACIQQILLSILKYYNQVVLKNIKSSKESREFYYNFCKYNQVIWLSYTEINHCFGLLLLLVTGLILLITPSGPFYLVSTIFEGRFRQNWQFSLMSFTAILWSLPWIVLLVLAMGRNDVQKEANKTAKMLTKVPRTGTGLDRMIEKFLLKNLRQKPILTAYGFFALDKSTLFKLFTAIFTYMVILVQFKEMENSTKSINKF Gr39D2dMSKVCRDLRIYLRLLHIMGMMCWHFDSDHCQLVATSGSERYAVVYAGCILVSTTAGF (SEQ ID NO:33)IFALLHPSRFHIAIYNQTGNFYEAVIFRSTCVVLFLVYVILYAWRHRYRDLVQHILRLNRRCASSCTNQQFLHNIILYGMLTILCFGNYLHGYTRAGLATLPLALCMLVYIFAFLVLCLLLMFFVSLKQVMTAGLIHYNQQLCQGDLISGLRGRQQILKLCGGELNECFGLLMLPIVALVLLMAPSGPFFLISTVLEGKFRPDECLIMLLTSSTWDTPWMIMLVLMLRTNGISEEANKTAKMLTKVPRTGTGLDRMIEKFLLKNLRQKPILTAYGFFALDKSTLFKLFTAIFTYMVILVQFKEMENSTKSINKF Gr43C1MKSATSKVVTALDVSVVVMAIVSGVYCGLFSLNDTLELNDRLNKIDNTLNAYNNFRRD (SEQ IDNO:34) RWRALGMAAVSLLAISILVGLDVGTWMRIAQDMNIAQSDTELNVHWYIPFYSLYFILTGLQVNIANTAYGLGRRFGRLNRMLSSSFLAENNATSAIKPQKVSTVKNVSVNRPAMPSALHASLTKLNGETLPSEAAGDKAAARSLILNVELLKLGYFPAKNKGLLLKSLADSHESLGKCVHLLSNSFGIAVLFILVSCLLHLVATAYFLFLELLSKRDNGYLWVQMLWICFHFLRLLMVVEPCHLAARESRKTIQIVCEIERKVHEPILAEAVKKFWQQLLWDADFSACGLCRVNRTILTSFASAIATYLVILIQFQRTNG Gr47A1MAFTSSQLCSLLTKFTALNGLNTYYFDTKTNAFRVSSKLKIYCAIHHALCVLALAHMS (SEQ IDNO:35) YSTATNLRVSVTVLTIGGTMACCVKSCWEKAQGIRNLARGLVTMEQKYFAGRPSGLLLKCRYYIKITFGSITLLRIHLIQPIYMRRLLPSQFYLNVGAYWLLYNMLLAAVLGFYFLLWEMCRIQKLINDQMTLILARSGQRNRLKKMQHCLRLYSKLLLLCDQFNSQLGHVAIWVLACKSWCQITFGYEIFQMVAAPKSIDLTMSMRVFVIFTYIFDAMNLFLGTDISELFSTFRADSQRILRETSRLDRLLSMFALKLALHPKRVVLLNVFTFDRKLTLTLLAKSTLYT ICCLQNDYNKLKAGr58A1 MLLKFMYIYGIGCGLMPAPLKKGQFLLGYKQRWYLIYTACLHGGLLTVLPFTFPHYMY (SEQID NO:36) DDSYMSSNPVLKWTFNLTNITRIMAMFSGVLLMWFRRKRILNLGENLILHCLKCKTLDNRSKKYSKLRKRVRNVLFQMLLVANLSILLGALILFRIHSVQRISKTAMIVAHITQFIYVVFMMTGICVILLVLHWQSERLQIALKDLCSFLNHEERNSLTLSENKANRSLGKLAKLFKLFAENQRLVREVFRTFDLPIALLLLKMFVTNVNLVYHGVQFGNDTIETSSYTRIVGQWVVISHYWSAVLLMNVVDDVTRRSDLKMGDLLREFSHLELVKRDFHLQLELFSDHLRCHPSTYKVCGLFIFNKQTSLAYFFYVLVQVLVLVQFDLKNKVEKR N Gr58A2MLHPKLGRVMNVVYYHSVVFALMSTTLRIRSCRKCLRLEKVSRTYTIYSFFVGIFLFLN (SEQ IDNO:37) LYFMVPRIMEDGYMKYNIVLQWNFFVMLFLRAIAVVSCYGTLWLKRHKIIQLYKYSLIYWKRFGHITRAIVDKKELLDLQESLARIMIRKIILLYSAFLCSTVLQYQLLSVINPQIFLAFCARLTHFLHFLCVKMGFFGVLVLLNHQFLVIHLAINALHGRKARKKWKALRSVAAMHLKTLRLARRIFDMFDIANATVFINMFMTAINILYHAVQYSNSSIKSNGWGILFGNGLIVFNFWGTMALMEMLDSVVTSCNNTGQQLRQLSDLPKVGPKMQRELDYFTMQLRQNRLVYKICGIVELDKPACLSYIGSILSNVIILMQFDLRRQRQPINDRQYLIHLMKNKTKV Gr58A3MNQYFLLHTYFQVSRLIGLCNLHYDSSNHRFILNHVPTVVYCVILNVVYLLVLPFALF (SEQ IDNO:38) VLTGNIYHCPDAGMFGVVYNVVALTKLLTMLFLMSSVWIQRRRLYKLGNDLMKMLHKFRFNLGNDCRNRCLCKGLLTSSRFVLLTQQLLTRDSVVNCESNSSLRQAMVPYQSAAIVYALIMILLMSYVDMTVYMVEVAGNWLLVNMTQGVREMVQDLEVLPERNGIPREMGLMQILAAWRKLWRRCRRLDALLKQFVDIFQWQVLFNLLTTYIFSIAVLFRLWIYLEFDKNFHLWKGILYAIIFLTHHVEIVMQFSIFEINRCKWLGLLEDVGNLWDINYSGRQCIKSSGTILSRKLEFSLLYMNRKLQLNPKRVRRLHIVGLFDISNLTVHNMTRSIITNVLVLCQI AYKKYG Gr59D1MADLLKLCLRIAYAYGRLTGVINFKIDLKTGQALVTRGATLISVSTHLLIFALLLYQT (SEQ IDNO:39) MRKSVVNVMWKYANSLHEYVFLVIAGFRVVCVFLELVSRWSQRRTFVRLFNSFRRLYQRNPDIIQYCRRSIVSKFFCVTMTETLHIIVTLAMMRNRLSIALALRIWAVLSLTAIINVIITQYYVATACVRGRYALLNKDLQAIVTESQSLVPNGGGVFVTKCCYLADRLERIAKSQSDLQELVENLSTAYEGEVVCLVITYYLNMLGTSYLLFSISKYGNFGNNLLVIITLCGIVYFVFYVVDCWINAFNVFYLLDAHDKMVKLLNKRTLFQPGLDHRLEMVFENFALNLVRNPLKLHMYGLFEFGRGTSFAVFNSLLTHSLLLIQYDVQNF Gr59D2MVDLVKTILLIAYWYGLAVGVSNFEVDWLTGEAIATRRTTIYAAVHNASLITLLILFN (SEQ IDNO:40) LGNNSLKSEFISARYLHEYFFMLMTAVRISAVLLSLITRWYQRSRFIRIWNQILALVRDRPQVVRGRWYRRSIILKFVFCVLSDSLHTISDVSAQRKRITADLIVKLSLLATLTTIFNMIVCQYYLAMVQVIGLYKILLQDLRCLVRQAECICSIRNRRGGVYSIQCCSLADQLDLIAERHYFLKDRLDEMSDLFQIQSLSMSLVYFFSTMGSIYFSVCSILYSSTGFGSTYWGLLLIVLSTASFYMDNWLSVNIGFHIRDQQDELFRVLADRTLFYRELDNRLEAAFENFQLQLASNRHEFYVMGLFKMERGRLIAMLSSVITHTMVLVQWEIQN Gr59E1MRSSATKGAKLKNSPRERLSSFNPQYAERYKELYRTLFWLLLISVLANTAPITILPGC (SEQ IDNO:41) PNRFYRLVHLSWMILWYGLFVLGSYWEFVLVTTQRVSLDRYLNAIESAIYVVHIFSIMLLTWQCRNWAPKLMTNIVTSDLNRAYTIDCNRTKRFIRLQLFLVGIFACLAIFFNIWTHKFVVYRSILSINSYVMPNIISSISFAQYYLLLQGIAWRQRRLTEGLERELTHLHSPRISEVQKIRMHHANLIDFTKAVNRTFQYSILLLFVGCFLNFNLVLFLVYQGIENPSMADFTKWVCMLLWLAMHVGKVCSILHFNQSIQNEHSTCLTLLSRVSYARKDIQDTITHFIIQMRTNVRQHVVCGVINLDLKFLTTLLVASADFFIFLLQYDVTYEALSKSVQGNVTRY Gr59E2MDSSYWENLLLTINRFLGVYPSGRVGVLRWLHTLWSLFLLMYIWTGSIVKCLEFTVEI (SEQ IDNO:42) PTIEKLLYLMEFPGNMATIAILVYYAVLNRPLAHGAELQIERIITGLKGKAKRLVYKRHGQRTLHLMATTLVFHGLCVLVDVVNYDFEFWTTWSSNSVYNLPGLMMSLGVLQYAQPVHFLWLVMDQMRMCLKELKLLQRPPQGSTKLDACYESAFAVLVDAGGGSALMIEEMRYTCNLIEQVHSQFLLRFGLYLVLNLLNSLVSICVELYLIFNFFETPLWEESVLLVYRLLWLAMHGGRIWFILSVNEQILEQKCNLCQLLNELEVCSSRLQRTINRFLLQLQRSIDQPLEACGIVTLDTRSLGGFIGVLMAIVIFLIQIGLGNKSLMGVALNRSNWVYV Gr68D1MKIYQDIYPISKPSQIFAILPFYSGDVDDGFRFGGLGRWYGRLVALIILTGSLTLGED (SEQ IDNO:43) VLFASKEYRLVASAQGDTEEINRTIETLLCIISYTMVVLSSVQNASRHFRTLHDIAKIDEYLLANGFRETYSCRNLTILVTSAAGGVLAVAFYYIHYRSGIGAKRQIILLLIYFLQLLYSTLLALYLRTLMMNLAQRIGFLNQKLDTFNLQDCGHMENWRELSNLIEVLCKFRYITENINCVAGVSLLFYFGFSFYTVTNQSYLAFATLTAGSLSSKTEVADTIGLSCIWVLAETITMIVICSACDGLASEVNGTAQILARIYGKSKQFQNLIDKFLTKSIKQDLQFTAYGFFSIDNSTLFKIFSAVTTYLVILIQFKQLEDSKNLSRSYQLVM Gr77E1MPRWLQLPGMSALGILYSLTRVFGLMATANWSPRGIKRVRQSLYLRIHGCVMLIFVGC (SEQ IDNO:44) FSPFAFWCIFQRMAFLRQNRILLMIGFNRYVLLLVCAFMTLWIHCFKQAEIIGCLNRLLKCRRRLRRLMHTRKLKDSMDCLATKGHLLEVVVLLSSYLLSMAQPIQILKDDPEVRRNFMYACSLVFVSVCQAILQLSLGMYTMAILFLGHLVRHSNLLLAKILADAEHIFESSQKAGFWPNRQELYKGQQKWLALELWRLLHVHHQLLKLHRSICSLCAVQAVCFLGFVPLECTIHLFFTYFMKYSKFILRKYGRSFPLNYFAIAFLVGLFTNLLLVILPTYYSERRFNCTREIIKGGGLAFPSRITVKQLRHTMHFYGLYLKNVEHVFAVSACGLFKLNNAILFCIVGAILEYLMILIQFDKVLN b) Previously reported partial Gustatory Receptorsequences. Predicted proteins have been extended as disclosed in thesubject application; extended sequence information is indicated in boldfont. Gr28A1 CQLLNGYRTEHAGGNYLLASDFDRRLKVFLQWKTSDSAESASGRLGSQYTFVGHKKKQ(SEQ ID NO:45) TGLTIKLAENGFCCWVLLLRYFSVLIKIVKYKIP Gr57B1MAVLYFFREPETVFDCAAFICILQFLMGCNGFGIRRSTFRISWASRIYSMSVAIAAFC (SEQ IDNO:46) CLFGSLSVLLAEEDIRERLAKADNLVLSISALELLMSTLVFGVTVISLQVFARRHLGIYQRLAALDARLMSDFGANLNYRKMLRKNIAVLGIVTTIYLMAINSAAVQVASGHRALFLLFALCYTIVTGGPHFTGYVHMTLAEMLGIRFRLLQQLLQPEFLNWRFPQLHVQELRIRQVVSMIQELHYLIQEINRVYALSLWAAMAHDLAMSTSELYILFGQSVGIGQQNEEENGSCYRMLGYLALVMIPPLYKLLIAPFYCDRTIYEARRCLRLVEKLDDWFPQKSSLRPLVESLMSWRIQAKIQFTSGLDVVLSRKVIGLFTSILVNYLLILIQFAMTQKMGEQIEQQ KIALQEWIGFGr65C1 MRVHQRQSAVIIQMGHPPFMSLKGGKSGFGSIVWPSAMREVNLLNRFTRQFLFLIVL (SEQ IDNO:47) VTQICGVATFVYNSKAQCFRQSGFLRFYSSLVLIFLALFLIVTTSKMFHNLQAVWPYVVGSVIILVVRIHGLLESAEIVELLNQMLRIMRQVNLMARHPNLFRLKHLLLLLLALQNLLRSLNTIVGISNHSAEAYDSFLNSVILLIILAVLLSFLLQITINICLFVVLIATYSELHHCTRRISNDMDKLRLHSVHESGQFMVLVKQLQGITEKLIRLRQNVFHITVRIIRHFRFHWLCAIIYGLLPFFSLTAKDQNGFNFLIISALNIIFQWTIFAILSRES Gr93F1MTGKRAESWSRLLLLWLYRCARGLLVLSSSLDRDKLQLKATKQGSRNRFLHILWRCI (SEQ ID NO:48)VVMIYAGLWPMLTSAVIGKRLESYADVLALAQSMSVSILAVISFVIQARGENQFREVLNRYLALYQRICLTTRLRHLFPTKFVVFFLLKLFFTLCGCFHEIIPLFENSHFDDISQMVGTGFGIYHWLGTLCVLDACFLGFLVSGILYEHMANNIIAMLKRMEPIESQDERYRMTKYRRMQLLCDFADELDECAAIYSELYHVTNSFRRILQWQILFYIYLNFINICLMLYQYILHFLNDDEVVFVSIVMAFVKLANLVLLMMCADYTVRQSEVPKKLPLDIVCSDMDERWDKSVSLLLFETFLGQLQTQRLEIKVLGFFHLNNEFILLILSAIISYLFILIQFGITGGFEASEDIKNFAD Gr93F2MQFWFGEELINLVNRFLQLFRRMQSLTNSPKNRFGDRAEFLLMFSKVFSLLFVFMAF (SEQ ID NO:49)RLMLSPWFLLTLVCDLYTSVGTGMITHLCFVGYLSIGVLYRDLNNYVDCQLRAQLRSLNGENNSFRNNPQPTRQAISNLDKCLYLYDEIHQVSRSFQQLFDLPLFLSLAQSLLAMSMVSYHAILRRQYSFNLWGLVIKLLIDVVLLTMSVHSAVNGSRLIRRLSFENFYVTDSQSYHQKVSPGAIILRIKYNTFPILQLELFLGRLQHQELRVFPLGLFEVSNELTLF FLSAMVTYLVFLVQGr93F3 MIERLKKVSLPALSAFILFCSCHYGRILGVICFDIGQRTSDDSLVVRNRHQFKWFCL (SEQ IDNO:50) SCRLISVTAVCCFCAPYVADIEDPYERLLQCFRLSASLICGICIIVVQVCYEKELLRMIISFLRLFRRVRRLSSLKRIGFGGKREFFLLLFKFICLVYELYSEICQLWHLPDSLSLFATLCEIFLEIGSLMIIHIGFVGYLSVAALYSEVNSFARIELRRQLRSLERPVGGPVGRKQLRIVEYRVDECISVYDEIERVGRTFHRLLELPVLIILLGKIFATTILSYEVIIRPELYARKIGMWGLVVKSFADVILLTLAVHEAVSSSRMMRRLSLENFPITDHKAWHMKVSDLMVFLIKCIFFSRLQWEMFLSRLNFFEFRVRPLGLFEVSNEVILLFLSSMI TYFTYVVQGr93F4 MSFYARFLSLVCFRLRKQKDNNVWLEEIWSNRSRWKWISVTLRIVPLCIYAFTYAEW (SEQ IDNO:51) ISNRMLITEKFLHSCSLVVSIPCYLSIIHLKICHGPEVTKLVNQYLHIFRLGTLDIRRRSQFGGGRELFLLILSVCCQIHEYVFILVIASRLCGFQHIIWWVSYTYVFIICNSIMCFGFIWHLSLGVLYAELNDNLRFESGFQTAFLRKQQRIRVQKSMALFKEISSVVTSLQDIFNVHLFLSALLTLLQVLVVWYKMIIDLGFSDFRIWSFSLKNLIQTLLPVLAIQEAANQFKQTRERALDIFLVGKSKHWMKSVSKLINQGILQLIGLFNVSNELFLIIVSAMFCYLVFVTQCVIVYRRRYVI Gr94E1MDFTSDYAHRRMVKFLTIILIGFMTVFGLLANRYRAGRRERFRFSKANLAFASLWAIA (SEQ IDNO:52) FSLVYGRQIYKEYQEGQINLKDATTLYSYMNITVAVINYVSQMIISDHVAKVLSKPPFFDTLKEFRLDSRSLYISIVLALVKTVAFPLTIEVAFILQQRRQHPEMSLIWTLYRLFPLIISNFLNNCYFGAMVVVKEILYALNRRLEAQLQEVNLLQRKDQLKLYTKYYRMQRFCALADELDQLAYRYRLIYVHSGKYLTPMSLSMILSLICHLLGITVGFYSLYYAIADTLIMGKPYDGLGSLINLVFLSISLAEITLLTHLCNHLLVATRRSAVILQEMNLQHADSRYRQAVHGFTLLVTVTKYQIKPLGLYELDMRLISNVFSAVASFLLILVQADLSQRFKMQ Gr97D1MRFLRRQTRRLRSIWQRSLPVRFRRGKLHTQLVTICLYATVFLNILYGVYLGRFSFRR (SEQ IDNO:53) KKFVFSKGLTIYSLFVATFFALFYIWNIYNEISTGQINLRDTIGIYCYMNVCVCLFNYVTQWEKTLQIIRFQNSVPLFKVLDSLDISAMIVWRAFIYGLLKIVFCPLITYITLILYHRRSISESQWTSVTTTKTMLPLIVSNQINNCFFGGLVLANLIFAAVNRKLHGIVKEANMLQSPVQMNLHKPYYRMRRFCELADLLDELARKYGFTASRSKNYLRFTDWSMVLSMLMNLLGITMGCYNQYLAIADHYINEEPFDLFLAIVLVVFLAVPFLELVMVARISNQTLVE VIVI Gr98B1IERFVCAQLVHEAYKQFASNGFRFLDALGCYEHSALGRARPLSRRGYAIKVSDHPATP (SEQ IDNO:54) PHYHMPPPKQPPSHLAVQHATLTSGLRQLSFSCVNCNCSRCCWSLPMHFRYIFNASLCNCQRQ*GY*TLSCRRHCTATKNISFSFCHISFVFLLKYDPKNPQLR GrLU1 = Gr36B1MFDWVGLLLKVLYYYGQIIGLINFEIDWQRGRVVAAQRGILFAIAINVLICMVLLLQI (SEQ IDNO:55) SKKFNLDVYFGRANQLHQYVIIVMVSLRMASLNRWRQRAQLMRLVECVLRLFLKKPHVKQMSRWAILVKFSVGVVSNFLQMAISMESLDRLGFNEFVGMASDFWMSAIINMAISQHYLVILFVRAYYHLLKTEVRQAIHESQMLSEIYPRRAAFMTKCCYLADRIDNIAKLQNQLQSIVTQLNQVFGIQGIMVYGGYYIFSVATTYITYSLAINGIEELHLSVRAAALVFSWFLFYYTSAILNLFVMLKLFDDHKEMERILEERTLFTSALDVRLEQSVSFYPTITELKYRDLVLSQFESIQLQLIRNPLKIEVLDIFTITRSSSAAMIGSIITNSIFLIQYDMEYF GrLU2 = Gr28A3MWLLRRSVGKSGNRPHDVYTCYRLTIFMALCLGIVPYYVSISSEGRGKLTSSYIGYIN (SEQ IDNO:56) IIIRMAIYMVNSFYGAVNRDTLMSNFFLTDISNVIDALQKINGMLGIFAILLISLLNRKELLKLLATFDRLETEAFPRVLKNLAHQWDTRSLKAVNQKQRSLQCLDSFSMYTIVTKDPAEIIQESMEIHHLICEAAATANKYFTYQLLTIISIAFLIIVFDAYYVLETLLGKSKRESKFKTVEFVTFFSCQMILYLIAIISIVEGSNRAIKKSEKTGGIVHSLLNKTKSAEVKEKLQQFSMQLMHLKINFTAAGLFNIDRTLYFTISGALTTYLIILLQFTSNSPNNGYGNGSSCCETFNNMTNHTL GrLU3 = Gr64A1MKGPNLNFRKTPSKDNGVKQVESLARPETPPPKFVEDSNLEFNVLASEKLPNYTNLDL (SEQ IDNO:57) FHRAVFPFMFLAQCVAIMPLVGIRESNPRRVRFAYKSIPMFVTLIFMIATSILFLSMFTHLLKIGITAKNFVGLVFFGCVLSAYVYFIRLAKKWPAVVRIWTRTEIPFTKPPYEIPKRNLSRRVQLAALAIIGLSLGEHALYQVSAILSYTRRIQMCANITTVPSFNNYMQTNYDYVFQLLPYSPIIAVLILATCTFVWNYMDLFIMMISKGLSYRFEQITTRIRKLEHEEVCESVFIQIREHYVKMCELLEFVDSAMSSLILLSCVNNLYFVCYQLLNVFNKLRWPINYIYFWYSLLYLIGRTAFVFLTAADINEESKRGLGVLRRVSSRSWCVEVERLIFQMTTQTVALSGKKFYFLTRRLLFGMAGTIVTYELVLLQFDEPNRRKGLQP GrLU4IYILSLYIFFQFISNVSLIVVLKLFRDI (SEQ ID NO:58) GrLU7 = Gr5A1MRQLKGRNRCNRAVRHLKVQGKMWLKNLKSGLEQIRESQVRGTRKNFLHDGSFHEAV (SEQ ID NO:59)APVLAVAQCFCLMPVCGISAPTYRGLSFNRRSWRFWYSSLYLCSTSVDLAFSIRRVAHSVLDVRSVEPIVFHVSILIASWQFLNLAQLWPGLMRHWAAVERRLPGYTCCLQRARPARRLKLVAFVLLVVSLMEHLLSIISVVYYDFCPRRSDPVESYLLGASAQLFEVFPYSNWLAWLGKIQNVLLTFGWSYMDIFLMMLGMGLSEMLARLNRSLEQQVRQPMPEAYWTWSRTLYRSIVELIREVDDAVSGIMLISFGSNLYFICLQLLKSINTMPSSAHAVYFYFSLLFLLSRSTAVLLFVSAINDQAREPLRLLRLVPLKGYHPEVFRFAAELASDQVALTGLKFFNVTRKLFLAMAGTVATYELVLIQFHEDKKTWDCSPFNLD

[0138] The family of receptors disclosed herein has a signature motifwhich comprises consecutive amino acids having the following sequence:

[0139] -G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQID NO: 60),

[0140] where X is any amino acid, and / means or.

[0141] The invention provides an isolated nucleic acid encoding aninsect gustatory receptor protein, wherein the receptor proteincomprises seven transmembrane domains and a C-terminal domain, and theC-terminal domain comprises consecutive amino acids having the followingsequence:

[0142] -G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQID NO: 60),

[0143] where X is any amino acid, and / means or.

[0144] The invention provides an isolated nucleic acid encoding aninsect odorant receptor protein, wherein the receptor protein comprisesseven transmembrane domains and a C-terminal domain, and the C-terminaldomain comprises consecutive amino acids having the following sequence:

[0145] -G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQID NO: 60),

[0146] where X is any amino acid, and / means or.

[0147] The invention provides an isolated nucleic acid molecule encodingan insect gustatory receptor protein, wherein the nucleic acid moleculeencodes a protein selected from the group consisting of:

[0148] (a) an insect gustatory receptor protein comprising consecutiveamino acids having the sequence of any of the receptors disclosedherein;

[0149] (b) an insect gustatory receptor protein which shares from 7-50%amino acid identity with any one of the proteins of (a), and comprisesseven transmembrane domains and a C-terminal domain, wherein theC-terminal domain comprises consecutive amino acids having the followingsequence:

[0150] -G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQID NO: 60),

[0151] where X is any amino acid, and / means or.

[0152] The invention provides an isolated nucleic acid molecule encodingan insect odorant receptor protein, wherein the nucleic acid moleculeencodes a protein selected from the group consisting of:

[0153] (a) an insect odorant receptor protein comprising consecutiveamino acids having the sequence of any of the receptors disclosedherein;

[0154] (b) an insect odorant receptor protein which shares from 7-50%amino acid identity with any one of the proteins of (a), and comprisesseven transmembrane domains and a C-terminal domain, wherein theC-terminal domain comprises consecutive amino acids having the followingsequence:

[0155] -G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQID NO: 60),

[0156] where X is any amino acid, and / means or.

[0157] The invention provides an isolated nucleic acid encoding aninsect gustatory receptor protein, wherein the nucleic acid moleculeencodes a protein selected from the group consisting of:

[0158] (a) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2B1 in SEQ ID NO: 1,

[0159] (b) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr8D1 in SEQ ID NO: 2,

[0160] (c) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr10B1 in SEQ ID NO:3,

[0161] (d) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr10B2 in SEQ ID NO:4,

[0162] (e) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr28A2 in SEQ ID NO:5,

[0163] (f) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr28A4 in SEQ ID NO:6,

[0164] (g) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr33C1 in SEQ ID NO:7,

[0165] (h) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr36B2 in SEQ ID NO:8,

[0166] (i) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr36B3 in SEQ ID NO:9,

[0167] (j) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr59C1 in SEQ ID NO:10,

[0168] (k) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr61D1 in SEQ ID NO:11,

[0169] (l) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr63F1 in SEQ ID NO:12,

[0170] (m) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr64A2 in SEQ ID NO:13,

[0171] (n) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for GR64A3 in SEQ ID NO:14,

[0172] (o) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr66C1 in SEQ ID NO:15,

[0173] (p) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr92D1 in SEQ ID NO:16,

[0174] (q) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr98A1 in SEQ ID NO:17,

[0175] (r) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr98A2 in SEQ ID NO:18,

[0176] (s) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.1 in SEQ ID NO:19,

[0177] (t) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.2 in SEQ ID NO:20,

[0178] (u) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.3 in SEQ ID NO:21,

[0179] (v) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.4 in SEQ ID NO:22,

[0180] (w) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.5 in SEQ ID NO:23,

[0181] (x) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr57B1 in SEQ ID NO:46,

[0182] (y) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr93F1 in SEQ ID NO:48,

[0183] (z) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr93F2 in SEQ ID NO:49,

[0184] (aa) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr93F3 in SEQ IDNO: 50,

[0185] (bb) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr93F4 in SEQ IDNO: 51,

[0186] (cc) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr94E1 in SEQ IDNO: 52,

[0187] (dd) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr93D1 in SEQ IDNO: 53,

[0188] (ee) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU1=Gr36B1 inSEQ ID NO: 55,

[0189] (ff) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU2=Gr28A3 inSEQ ID NO: 56,

[0190] (gg) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU3=Gr64A1 inSEQ ID NO: 57,

[0191] (hh) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU7=Gr5A1 inSEQ ID NO: 59, and

[0192] (ii) an insect gustatory receptor protein which shares from 7-50%amino acid identity with any one of the proteins of (a)-(hh), andcomprises seven transmembrane domains and a C-terminal domain, whereinthe C-terminal domain comprises consecutive amino acids having thefollowing sequence:

[0193] -G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQID NO: 60),

[0194] where X is any amino acid, and / means or.

[0195] In one embodiment, the insect odorant receptor protein shares atleast 20% amino acid identity with any one of the proteins describedherein. In one embodiment, the insect odorant receptor protein shares atleast 30% amino acid identity with any one of the proteins describedherein. In one embodiment, the insect odorant receptor protein shares atleast 40% amino acid identity with any one of the proteins describedherein. In one embodiment, the insect odorant receptor protein shares atleast 50% amino acid identity with any one of the proteins describedherein. In one embodiment, the insect odorant receptor protein shares atleast 60% amino acid identity with any one of the proteins describedherein. In one embodiment, the insect odorant receptor protein shares atleast 70% amino acid identity with any one of the proteins describedherein. In one embodiment, the insect odorant receptor protein shares atleast 80% amino acid identity with any one of the proteins describedherein.

[0196] The invention provides an isolated nucleic acid molecule encodingan insect odorant receptor protein, wherein the nucleic acid moleculeencodes a protein selected from the group consisting of:

[0197] (a) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2B1 in SEQ ID NO: 1,

[0198] (b) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr8D1 in SEQ ID NO: 2,

[0199] (c) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr10B1 in SEQ ID NO:3,

[0200] (d) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr10B2 in SEQ ID NO:4,

[0201] (e) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr28A2 in SEQ ID NO:5,

[0202] (f) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr28A4 in SEQ ID NO:6,

[0203] (g) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr33C1 in SEQ ID NO:7,

[0204] (h) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr36B2 in SEQ ID NO:8,

[0205] (i) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr36B3 in SEQ ID NO:9,

[0206] (j) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr59C1 in SEQ ID NO:10,

[0207] (k) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr61D1 in SEQ ID NO:11,

[0208] (l) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr63F1 in SEQ ID NO:12,

[0209] (m) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr64A2 in SEQ ID NO:13,

[0210] (n) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for GR64A3 in SEQ ID NO:14,

[0211] (o) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr66C1 in SEQ ID NO:15,

[0212] (p) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr92D1 in SEQ ID NO:16,

[0213] (q) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr98A1 in SEQ ID NO:17,

[0214] (r) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr98A2 in SEQ ID NO:18,

[0215] (s) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.1 in SEQ ID NO:19,

[0216] (t) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.2 in SEQ ID NO:20,

[0217] (u) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.3 in SEQ ID NO:21,

[0218] (v) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.4 in SEQ ID NO:22,

[0219] (w) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr2940.5 in SEQ ID NO:23,

[0220] (x) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr57B1 in SEQ ID NO:46,

[0221] (y) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr93F1 in SEQ ID NO:48,

[0222] (z) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for Gr93F2 in SEQ ID NO:49,

[0223] (aa) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr93F3 in SEQ IDNO: 50,

[0224] (bb) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr93F4 in SEQ IDNO: 51,

[0225] (cc) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr94E1 in SEQ IDNO: 52,

[0226] (dd) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for Gr93D1 in SEQ IDNO: 53,

[0227] (ee) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU1=Gr36B1 inSEQ ID NO: 55,

[0228] (ff) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU2=Gr28A3 inSEQ ID NO: 56,

[0229] (gg) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU3=Gr64A1 inSEQ ID NO: 57,

[0230] (hh) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU7=Gr5A1 inSEQ ID NO: 59, and

[0231] (ii) an insect odorant receptor protein which shares from 7-50%amino acid identity with any one of the proteins of (a)-(hh), andcomprises seven transmembrane domains and a C-terminal domain, whereinthe C-terminal domain comprises consecutive amino acids having thefollowing sequence:

[0232] -G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQID NO: 60),

[0233] where X is any amino acid, and / means or.

[0234] In one embodiment, the insect gustatory receptor protein sharesat least 20% amino acid identity with any one of the proteins describedherein. In one embodiment, the insect gustatory receptor protein sharesat least 30% amino acid identity with any one of the proteins describedherein. In one embodiment, the insect gustatory receptor protein sharesat least 40% amino acid identity with any one of the proteins describedherein. In one embodiment, the insect gustatory receptor protein sharesat least 50% amino acid identity with any one of the proteins describedherein. In one embodiment, the insect gustatory receptor protein sharesat least 60% amino acid identity with any one of the proteins describedherein. In one embodiment, the insect gustatory receptor protein sharesat least 70% amino acid identity with any one of the proteins describedherein. In one embodiment, the insect gustatory receptor protein sharesat least 80% amino acid identity with any one of the proteins describedherein.

[0235] In one embodiment of any of the isolated nucleic acid moleculesdescribed herein, the insect gustatory or odorant receptor proteincomprises seven transmembrane domains.

[0236] In different embodiments of any of the isolated nucleic acidmolecules described herein, the nucleic acid is DNA or RNA. In differentembodiments, the DNA is cDNA, genomic DNA, or synthetic DNA.

[0237] In one embodiment of any of the isolated nucleic acid moleculesdescribed herein, the nucleic acid molecule encodes a Drosophilareceptor.

[0238] The nucleic acid molecules encoding an insect gustatory orodorant receptor include molecules coding for polypeptide analogs,fragments or derivatives of antigenic polypeptides which differ fromnaturally-occurring forms in terms of the identity or location of one ormore amino acid residues (deletion analogs containing less than all ofthe residues specified for the protein, substitution analogs wherein oneor more residues specified are replaced by other residues and additionanalogs where in one or more amino acid residues is added to a terminalor medial portion of the polypeptides) and which share some or allproperties of naturally-occurring forms.

[0239] These molecules include but not limited to: the incorporation ofcodons “preferred” for expression by selected non-mammalian hosts; theprovision of sites for cleavage by restriction endonuclease enzymes; andthe provision of additional initial, terminal or intermediate sequencesthat facilitate construction of readily expressed vectors. Accordingly,these changes may result in a modified insect receptor. It is the intentof this invention to include nucleic acid molecules which encodemodified insect receptors. Also, to facilitate the expression ofreceptors in different host cells, it may be necessary to modify themolecule such that the expressed receptors may reach the surface of thehost cells. The modified insect receptor should have biologicalactivities similar to the unmodified insect gustatory or odorantreceptor. The molecules may also be modified to increase the biologicalactivity of the expressed receptor.

[0240] The invention provides a nucleic acid molecule comprising atleast 12 nucleotides which specifically hybridizes with any of theisolated nucleic acid molecules described herein.

[0241] In one embodiment, the nucleic acid molecule hybridizes with aunique sequence within the sequence of any of the nucleic acid moleculesdescribed herein. In different embodiments, the nucleic acid is DNA,cDNA, genomic DNA, synthetic DNA, RNA, or synthetic RNA.

[0242] This invention provides a vector which comprises any of theisolated nucleic acid molecules described herein. In one embodiment, thevector is a plasmid.

[0243] In one embodiment of any of the vectors described herein, any ofthe isolated nucleic acid molecules described herein is operativelylinked to a regulatory element.

[0244] Regulatory elements required for expression include promotersequences to bind RNA polymerase and transcription initiation sequencesfor ribosome binding. For example, a bacterial expression vectorincludes a promoter such as the lac promoter and for transcriptioninitiation the Shine-Dalgarno sequence and the start codon AUG.Similarly, a eukaryotic expression vector includes a heterologous orhomologous promoter for RNA polymerase II, a downstream polyadenylationsignal, the start codon AUG, and a termination codon for detachment ofthe ribosome. Such vectors may be obtained commercially or assembledfrom the sequences described by methods well-known in the art, forexample the methods described herein for constructing vectors ingeneral.

[0245] The invention provides a host vector system for production of apolypeptide having the biological activity of an insect gustatory orodorant receptor, which comprises any of the vectors described hereinand a suitable host. In different embodiments, the suitable host is abacterial cell, a yeast cell, an insect cell, or an animal cell.

[0246] The host cell of the expression system described herein may beselected from the group consisting of the cells where the protein ofinterest is normally expressed, or foreign cells such as bacterial cells(such as E. coli), yeast cells, fungal cells, insect cells, nematodecells, plant or animal cells, where the protein of interest is notnormally expressed. Suitable animal cells include, but are not limitedto Vero cells, HeLa cells, Cos cells, CV1 cells and various primarymammalian cells.

[0247] The invention provides a method of producing a polypeptide havingthe biological activity of an insect gustatory or odorant receptor whichcomprising growing any of the host vector systems described herein underconditions permitting production of the polypeptide and recovering thepolypeptide so produced.

[0248] The invention provides a purified insect gustatory or odorantreceptor protein encoded by any of the isolated nucleic acid moleculesdescribed herein. This invention further provides a polypeptide encodedby any of the isolated nucleic acid molecules described herein.

[0249] The invention provides an antibody which specifically binds to aninsect gustatory or odorant receptor protein encoded by any of theisolated nucleic acid molecules described herein. In one embodiment, theantibody is a monoclonal antibody. In another embodiment, the antibodyis polyclonal.

[0250] The invention provides an antibody which competitively inhibitsthe binding of any of the antibodies described herein capable ofspecifically binding to an insect gustatory or odorant receptor. In oneembodiment, the antibody is a monoclonal antibody. In anotherembodiment, the antibody is polyclonal.

[0251] Monoclonal antibody directed to an insect gustatory or odorantreceptor may comprise, for example, a monoclonal antibody directed to anepitope of an insect gustatory or odorant receptor present on thesurface of a cell. Amino acid sequences may be analyzed by methods wellknown to those skilled in the art to determine whether they producehydrophobic or hydrophilic regions in the proteins which they build. Inthe case of cell membrane proteins, hydrophobic regions are well knownto form the part of the protein that is inserted into the lipid bilayerwhich forms the cell membrane, while hydrophilic regions are located onthe cell surface, in an aqueous environment.

[0252] Antibodies directed to an insect gustatory or odorant receptormay be serum-derived or monoclonal and are prepared using methods wellknown in the art. For example, monoclonal antibodies are prepared usinghybridoma technology by fusing antibody producing B cells from immunizedanimals with myeloma cells and selecting the resulting hybridoma cellline producing the desired antibody. Cells such as NIH3T3 cells or 293cells which express the receptor may be used as immunogens to raise suchan antibody. Alternatively, synthetic peptides may be prepared usingcommercially available machines.

[0253] As a still further alternative, DNA, such as a cDNA or a fragmentthereof, encoding the receptor or a portion of the receptor may becloned and expressed. The expressed polypeptide may be recovered andused as an immunogen.

[0254] The resulting antibodies are useful to detect the presence ofinsect gustatory or odorant receptors or to inhibit the function of thereceptor in living animals, in humans, or in biological tissues orfluids isolated from animals or humans.

[0255] This antibodies may also be useful for identifying or isolatingother insect gustatory or odorant receptors. For example, antibodiesagainst the Drosophila odorant receptor may be used to screen ancockroach expression library for a cockroach gustatory or odorantreceptor. Such antibodies may be monoclonal or monospecific polyclonalantibody against a selected insect gustatory or odorant receptor.Different insect expression libraries are readily available and may bemade using technologies well-known in the art.

[0256] One means of isolating a nucleic acid molecule which encodes aninsect gustatory or odorant receptor is to probe a libraries with anatural or artificially designed probes, using methods well known in theart. The probes may be DNA, cDNA or RNA. The library may be cDNA orgenomic DNA.

[0257] The invention provides a method of transforming a cell whichcomprises transfecting a host cell with any of the vectors describedherein.

[0258] The invention provides a transformed cell produced by any of themethods described herein. In one embodiment, prior to being transfectedwith the vector the host cell does not express a gustatory or an odorantreceptor protein. In one embodiment, prior to being transfected with thevector the host cell does not express a gustatory and an odorantreceptor protein. In one embodiment, prior to being transfected with thevector the host cell does express a gustatory or odorant receptorprotein.

[0259] This invention provies a method of identifying a compound whichspecifically binds to an insect gustatory receptor which comprisescontacting any of the transformed cells described herein, or a membranefraction from said cells, with the compound under conditions permittingbinding of the compound to the gustatory receptor, detecting thepresence of any such compound specifically bound to the receptor, andthereby identifying the compound as a compound which specifically bindsto an insect gustatory receptor.

[0260] This invention provides a method of identifying a compound whichspecifically binds to an insect odorant receptor which comprisescontacting any of the transformed cells described herein, or a membranefraction from said cells, with the compound under conditions permittingbinding of the compound to the odorant receptor, detecting the presenceof any such compound specifically bound to the receptor, and therebyidentifying the compound as a compound which specifically binds to aninsect odorant receptor.

[0261] This invention provides a method of identifying a compound whichspecifically binds to an insect gustatory receptor which comprisescontacting any of the purified insect gustatory receptor proteinsdescribed herein with the compound under conditions permitting bindingof the compound to the purified gustatory receptor protein, detectingthe presence of any such compound specifically bound to the receptor,and thereby identifying the compound as a compound which specificallybinds to an insect gustatory receptor.

[0262] This invention provides a method of identifying a compound whichspecifically binds to an insect odorant receptor which comprisescontacting any of the purified insect odorant receptor proteinsdescribed herein with the compound under conditions permitting bindingof the compound to the purified odorant receptor protein, detecting thepresence of any such compound specifically bound to the receptor, andthereby identifying the compound as a compound which specifically bindsto an insect odorant receptor.

[0263] In one embodiment, the purified insect gustatory or odorantreceptor protein is embedded in a lipid bilayer. The purified receptormay be embedded in the liposomes with proper orientation to carry outnormal functions. Liposome technology is well-known in the art.

[0264] The invention provides a method of identifying a compound whichactivates an insect gustatory receptor which comprises contacting any ofthe transformed cells described herein, or a membrane fraction from saidcells, with the compound under conditions permitting activation of thegustatory receptor, detecting activation of the receptor, and therebyidentifying the compound as a compound which activates an insectgustatory receptor.

[0265] The invention provides a method of identifying a compound whichactivates an insect odorant receptor which comprises contacting any ofthe transformed cells described herein, or a membrane fraction from saidcells, with the compound under conditions permitting activation of theodorant receptor, detecting activation of the receptor, and therebyidentifying the compound as a compound which activates an insect odorantreceptor.

[0266] The invention provides a method of identifying a compound whichactivates an insect gustatory receptor which comprises contacting any ofthe purified insect gustatory receptor proteins described herein withthe compound under conditions permitting activation of the gustatoryreceptor, detecting activation of the receptor, and thereby identify thecompound as a compound which activates an insect gustatory receptor.

[0267] The invention provides a method of identifying a compound whichactivates an insect odorant receptor which comprises contacting any ofthe purified insect odorant receptor proteins described herein with thecompound under conditions permitting activation of the odorant receptor,detecting activation of the receptor, and thereby identify the compoundas a compound which activates an insect odorant receptor.

[0268] In one embodiment, the purified insect gustatory or odorantreceptor protein is embedded in a lipid bilayer. The purified receptormay be embedded in the liposomes with proper orientation to carry outnormal functions. Liposome technology is well-known in the art.

[0269] The invention provides a method of identifying a compound whichinhibits the activity of an insect gustatory receptor which comprisescontacting any of the transformed cells described herein, or a membranefraction from said cells, with the compound under conditions permittinginhibition of the activity of the gustatory receptor, detectinginhibition of the activity of the receptor, and thereby identifying thecompound as a compound which inhibits the activity of an insectgustatory receptor.

[0270] The invention provides a method of identifying a compound whichinhibits the activity of an insect odorant receptor which comprisescontacting any of the transformed cells described herein, or a membranefraction from said cells, with the compound under conditions permittinginhibition of the activity of the odorant receptor, detecting inhibitionof the activity of the receptor, and thereby identifying the compound asa compound which inhibits the activity of an insect odorant receptor.

[0271] The invention provides a method of identifying a compound whichinhibits the activity of an insect gustatory receptor which comprisescontacting any of the purified insect gustatory receptor proteinsdescribed herein with the compound under conditions permittinginhibition of the activity of the gustatory receptor, detectinginhibition of the activity of the receptor, and thereby identifying thecompound as a compound which inhibits the activity of an insectgustatory receptor.

[0272] The invention provides a method of identifying a compound whichinhibits the activity of an insect odorant receptor which comprisescontacting any of the purified insect odorant receptor proteinsdescribed herein with the compound under conditions permittinginhibition of the activity of the odorant receptor, detecting inhibitionof the activity of the receptor, and thereby identifying the compound asa compound which inhibits the activity of an insect odorant receptor.

[0273] In one embodiment, the purified insect gustatory or odorantreceptor protein is embedded in a lipid bilayer. The purified receptormay be embedded in the liposomes with proper orientation to carry outnormal functions. Liposome technology is well-known in the art.

[0274] In one embodiment of any of the methods described herein, thecompound is not previously known.

[0275] The invention provides a compound identified by any of themethods described herein. In one embodiment, the compound is an alarmodorant ligand or a ligand associated with fertility. In one embodimentthe compound interferes with chemosensory perception.

[0276] The invention provides a method of combating ingestion of cropsby pest insects which comprises identifying a compound by any of themethods described herein and spraying the crops with the compound.

[0277] The invention provides a use of a compound identified by any ofthe methods described herein for combating ingestion of crops by pestinsects.

[0278] The invention provides a use of a compound identified by any ofthe methods described herein for combating pest nuisances anddisease-carrying insects by interfering with chemosensory perception.

[0279] The invention provides a method of combating disease-carryinginsects in an area which comprises identifying a compound by any of themethods described herein and spraying the area with the compound.

[0280] The invention provides a method of controlling a pest populationin an area which comprises identifying a compound any of the methodsdescribed herein and spraying the area with the compound. In oneembodiment, the compound is an alarm odorant ligand or a ligandassociated with fertility. In one embodiment the compound interfereswith chemosensory perception.

[0281] The invention provides a method of controlling a pest populationwhich comprises identifying a compound by any of the methods describedherein, wherein the compound interferes with an interaction between anodorant ligand and an odorant receptor which are associated withfertility.

[0282] The invention provides a composition which comprises a compoundidentified by any of the methods described herein and a carrier.

[0283] The invention provides a method of preparing a composition whichcomprises identifying a compound by any of the methods described hereinand admixing a carrier. The invention provides a method of preparing acomposition which comprises identifying a compound by any of the methodsdescribed herein, recovering the compound free from the receptor, andadmixing a carrier. The invention provides a method of preparing acomposition which comprises identifying a compound by any of the methodsdescribed herein, recovering the compound from the cells or membranefraction or receptor protein, and admixing a carrier. Examples ofcarriers include, but are not limited to, phosphate buffered saline,physiological saline, water, and emulsions, such as oil/water emulsions.

[0284] The invention provides a use of a compound identified by any ofthe methods described herein for preparing a composition for controllinga pest population in an area by spraying the area with the compound. Inone embodiment, the compound is an alarm odorant ligand or a ligandassociated with fertility. In one embodiment the compound interfereswith chemosensory perception.

[0285] The invention provides a use of a compound identified by any ofthe methods described herein for preparing a composition for controllinga pest population. In one embodiment, the compound interferes with aninteraction between an odorant ligand and an odorant receptor which areassociated with fertility. In one embodiment the compound interfereswith chemosensory perception.

[0286] This invention will be better understood from the ExperimentalProcedures which follow. However, one skilled in the art will readilyappreciate that the specific methods and results discussed are merelyillustrative of the invention as described more fully in the claimswhich follow thereafter.

[0287] Experimental Details

[0288] Materials And Methods

[0289] Experimental Animals

[0290] Drosophila stocks were reared on standard cornmeal-agar-molassesmedium at 25° C. Oregon R strains were used for in situ hybridizationexperiments, and yw or W1118 strains were used for transgene injections.P-element mediated germline transformations and all subsequent flymanipulations were performed using standard techniques (Rubin et al.,1985). In some cases, transgenic constructs were injected as mixtures oftwo constructs, and progeny of individual transformants were analyzed bypolymerase chain reaction (PCR) to determine their genotype. Allanalyses were performed on two to five independent transgenic lines foreach construct.

[0291] Identification of Additional GR Genes

[0292] A search for novel seven transmembrane domain receptors wasperformed among 5660 predicted Drosophila proteins of ‘unknown function’(Adams et al., 2000) using a transmembrane prediction program (TopPred)(von Heijne, 1992). 310 Drosophila genes were selected for in situhybridization analysis, 20 of which were novel members of the GR genefamily previously described (Clyne et al., 2000). Additional members ofthe GR gene family were identified using BLAST (Altschul et al., 1990)and hidden Markov model (Eddy, 1998) searches of Drosophila genomedatabases with existing GR members as templates. GRs were grouped intosubfamilies by BLASTP comparisons (Altschul, et al., 1998) with an evalue cutoff of 10⁻⁵. Sequence relationships between the GR gene familyand the DOR genes were analyzed with HMMs (Eddy, 1998), CLUSTALalignments and neighbor joining trees (Saitou and Nei, 1987; Higgins andSharp, 1988), and NxN BLASTP (Rubin et al., 2000) comparisons.

[0293] Five GR genes were isolated by PCR from proboscis cDNA usingprimers corresponding to the extent of the predicted coding region.Proboscis cDNA was obtained from one thousand microdissected probosces,using Dynal mRNA Direct (610.11) and Perkin-Elmer GeneAmp (N808-0017)kits. PCR products were cloned into pGEM-T (Promega) and sequenced intheir entirety, using ABI 310 or 377 sequencing systems. An antennalcDNA library (kindly provided by Dr. Leslie Vosshall) was screened(3×10⁶ inserts) with PCR probes for Gr63F1, Gr10B1, and Gr21D1, and 6independent cDNAS of Gr63F1 were isolated and sequenced. Sequences ofGr43C1, Gr47A1, Gr58A3, and Gr59E1 matched the previously reportedsequences (Clyne et al., 2000), and sequences of Gr10B1 and Gr63F1 areincluded in the list above.

[0294] In situ Hybridization

[0295] RNA in situ hybridization was performed as previously described(Vosshall et al., 1999). Riboprobes for the 56 GR genes were generatedfrom PCR products corresponding to predicted exons and ranged from300-800 bp in length. Newly eclosed flies were used for in situhybridization experiments because hybridization signals were found to bemore robust at this stage.

[0296] Construction of GR Transgenes

[0297] Generation of 15 GR promoter-Gal4 transgenes was performed aspreviously described (Vosshall et al., 2000). Briefly, sequencesimmediately adjacent to the predicted ATG initiation codon and avariable distance upstream were isolated by long range PCR with genomicDNA as template, and upstream elements were cloned into a modifiedCaSpeR-AUG-Gal4 vector (Vosshall et al., 2000). Regulatory elementlengths for each of the GR transgenes are as follows: Gr2B1, 2.240 kB;G21D1, 9.323 kB; Gr22B1, 8.249 kB; Gr28A3, 4.245 kB; Gr32D1, 3.776 kB;Gr47A1, 7.321 kB; Gr66C1, 3.153 kB and Gr5A1, 5.156 kB; Gr10B1, 0.656kB; Gr33C1, 3.315 kB; Gr39D2A, 8.227 kB; Gr59E2, 2.586 kB; Gr77E1, 9.502kB; Gr93F1, 9.368 kB; Gr98A1, 1.086 kB. The first 7 transgenes drivereporter expression in chemosensory tissues; the remaining 8 transgeneswere not detectably expressed in adults or larvae.

[0298] Visualization of lacZ, GFP, and nSyb-GFP reporters

[0299] GR promoter-Gal4 lines were crossed to UAS-LacZ stocks, and wholemount heads of progeny were examined for B-galactosidase activity,following existing staining procedures (Wang et al., 1998). To enhancevisualization of sensilla in the proboscis labellum, probosces werebisected and pseudotracheae were removed by microdissection. Images wererecorded using a Nikon SPOT-RT digital microscope system equipped withdifferential interference contrast.

[0300] Progeny resulting from crosses of GR promoter-Gal4 to UAS-GFPwere examined for GFP expression by direct flourescence microscopy.Adult organs and live larvae were mounted in glycerol using smallcoverslips as spacers and GFP flourescence was recorded with a BioRad1024 confocal microscope.

[0301] To visualize axonal projections of GR-bearing neurons, GRpromoter-Gal4 flies were mated with UAS-nSyb-GFP, and brains of F1progeny were examined by flourescent immunohistochemistry. Larval brainswere dissected and antibody staining was carried out as described in(Vosshall et al., 2000). Expression of nSyb-GFP was visualized with arabbit anti-GFP antibody (Molecular Probes) and a goat anti-rabbitsecondary antibody coupled to Alexa Fluor 488 (Molecular Probes). Thenc82 monoclonal antibody (Laissue et al., 1999) was used to label brainneuropil and was visualized with goat anti-mouse IgG coupled to CY3(Jackson ImmunoResearch). Cell nuclei were counterstained with TOTO-3(Molecular Probes). Images were analyzed with a BioRad 1024 confocalmicroscope.

[0302] Results

[0303] A Large Family of Candidate Chemoreceptors

[0304] A novel family of putative seven transmembrane domain proteinswas recently identified in searches of the Drosophila genome (Clyne etal., 2000). Analysis of a database representing 60% of the Drosophilagenome identified twenty-three full-length genes and 20 partialsequences. The expression of 19 genes was examined by RT-PCR analysisand revealed 18 transcripts in the proboscis labellum, suggesting thatthis novel gene family may encode the fly gustatory receptors (GRs). Theexpression of these genes was characterized by in situ hybridization andtransgene experiments and observe expression in both gustatory andolfactory chemosensory neurons in both larvae and adult flies.

[0305] The gene family has been extended by analyzing the recentlycompleted euchromatic genome sequence of Drosophila (Adams et al., 2000)using reiterative BLAST searches (Altschul et al., 1990), transmembranedomain prediction programs (von Heijne, 1992), and hidden Markov model(HMM) analyses (Eddy, 1998). These searches have identified a total of56 candidate GR genes in the Drosophila genome, including 23 GRs notpreviously described. As originally reported, these genes encodeputative seven transmembrane domain proteins of about 480 amino acids(Clyne et al., 2000). The family as a whole is extremely divergent andreveals an overall sequence identity ranging from 7-70%. However, allgenes share significant sequence similarity within a 33 amino signaturemotif in the putative seventh transmembrane domain in the C-terminus(FIG. 1). Analysis of the sequence of the 56 genes reveals the existenceof four discrete subfamilies (containing ten, six, four and three genes)whose members exhibit greater overall sequence identity ranging from40-70%. Twenty-two of the GR genes reside as individual sequencesdistributed throughout each of the Drosophila chromosomes, whereas theremaining genes are linked in the genome in small tandem arrays of twoto five genes.

[0306] The GR family shares little sequence similarity outside of theconserved C terminal signature in the putative seventh transmembranedomain and therefore searches of the genome database are unlikely to beexhaustive. Thus, this family of candidate gustatory receptors consistsof a minimum of 56 genes. Moreover, this analysis would not detectalternatively spliced transcripts, a feature previously reported forsome members of this gene family (Clyne et al., 2000). cDNAs or RT PCRproducts were identified from six genes; verification of the genepredictions therefore awaits the isolation and sequencing of additionalcDNAs.

[0307] Interestingly, the 33 amino acid signature motif characteristicof the GR genes is present but somewhat diverged in 33 of the 70 membersof the family of Drosophila odorant receptor (DOR) genes. (FIG. 1). TheDOR genes, however, possess additional conserved motifs not present inthe GR genes and define a distinct family (Clyne et al., 1999; Vosshallet al., 1999; Gao and Chess, 1999; Vosshall et al., 2000). Theseobservations suggest that the putative gustatory and olfactory receptorgene families may have evolved from a common ancestral gene.

[0308] GR Gene Expression in Olfactory and Gustatory Organs

[0309] Insight into the specific problem of the function of thesecandidate receptor genes and the more general question as to howtastants are recognized and discriminated by the fly brain initiallyrequires an analysis of the patterns of expression of the individual GRgenes in chemosensory cells. In situ hybridization was performed onsagittal sections of the adult fly head with RNA probes obtained fromall 56 family members. Six of the genes are expressed in discrete,topographically-restricted subpopulations of neurons within theproboscis (FIG. 2A). Three of the genes revealed no hybridization to theproboscis but are expressed in spatially-defined sets of neurons withinthe third antennal segment, the major olfactory organ of the adult fly(FIG. 2B). The remaining genes show no hybridization to adult headtissues.

[0310] Our analysis of the pattern of GR gene expression by in situhybridization demonstrates that a small number of GR genes istranscribed in either the proboscis or the antenna, suggesting that thisfamily encodes chemosensory receptors involved in smell as well astaste. However, expression of over 80% of the family members was notdetected using these in situ hybridization conditions. The sequence ofthese GR genes does not reveal nonsense or frameshift mutations thatcharacterize pseudogenes. The inability to detect transcripts from themajority of the GR genes by in situ hybridization might result from lowlevels of expression of GR genes, expression in populations ofchemosensory cells not amenable to analysis by in situ hybridization(e.g., leg, wing, or vulva), or expression at other developmentalstages.

[0311] Lines of flies expressing GR promoter transgenes were thereforegenerated to visualize the expression in a wider range of cell typeswith higher sensitivity. Transgenes were constructed in which putativeGR promoter sequences (0.5-9.5 kb of DNA immediately upstream of thetranslational start) were fused to the Gal4 coding sequence (Brand andPerrimon, 1993). Flies bearing GR transgenes were mated to transgenicflies that contain either B-galactosidase (lacZ) or green fluorescentprotein (GFP) under the control of the Gal4-responsive promoter, UAS. GRpromoter-Gal4 lines were constructed with upstream sequences from 15chemoreceptor genes and transgene expression was detected for 7 lines(Table 1) Five of the genes that were expressed by transgene analyseswere also detected by in situ hybridization.

[0312] A Spatial Map of GR Expression in the Proboscis

[0313] Expression of the GR transgenes in the proboscis was initiallyvisualized using the UAS-lacZ reporter. The labellum of the proboscis isformed from the fusion of two labial palps, each containing 31-36bilaterally symmetric chemosensory bristles arranged in four rows (FIG.3) (Arora et al., 1987; Ray et al., 1993). The sensilla of the firstthree columns contains four chemosensory neurons and a singlemechanoreceptor cell whereas the sensilla in the most peripheral row arecomposed of only two chemosensory neurons and one mechanoreceptor (Nayakand Singh, 1983; Ray et al., 1993). Each labial palp therefore containsapproximately 120 chemosensory neurons.

[0314] The GR promoter-Gal4 lines were crossed to UAS-lacZ flies and theprogeny were examined for lacZ expression by staining of whole mountpreparations of the labial palp. Five transgenic lines exhibit lacZexpression in sensory neurons of the labial sensilla (FIG. 3). Theexpression of each transgene is restricted to a single row ofchemosensory bristles. Gr47A1, for example, is expressed in sensillainnervating the most peripheral row of bristles, whereas Gr66C1 isexpressed in sensilla that occupy the most medial column (FIG. 3). Fliesbearing a GR promoter-Gal4 gene were also crossed with UAS-GFP stocks.The expression of GFP allows greater cellular definition and revealsthat each receptor is expressed in a single neuron within a sensillum(FIG. 4A, 4B). The pattern of GR gene expression determined by GRpromoter transgenes resembles that seen by in situ hybridization.However, co-expression of the transgene reporter and the endogenous genecould not be directly demonstrated by dual label in situ hybridizationdue to low levels of GR gene expression. Nevertheless, this pattern ofexpression, in which a receptor is expressed in only one neuron in asensillum and in one sensillar row, is maintained in over 50 individualsexamined for each transgenic line and is also maintained in independenttransformed lines for each GR transgene.

[0315] Receptor Expression in Other Chemosensory Neurons

[0316] Chemosensory bristles reside at multiple anatomic sites in thefly including the taste organs in the mouth, the legs and wings, as wellas in the female genitalia (Table 1) (Stocker, 1994). Three sensoryorgans reside deep in the mouth: the labral sense organ (comprised of 10chemosensory neurons) and the ventral and dorsal cibarial organs (eachcontaining six chemosensory neurons) (Stocker and Schorderet, 1981;Nayak and Singh, 1983). The function of these specialized sensory organsis unknown, but their anatomic position and CNS projection patternsuggests that they participate in taste recognition (Stocker andSchorderet, 1981; Nayak and Singh, 1983). Three of the five GRpromoter-Gal4 lines that are expressed in the proboscis are alsoexpressed in the cibarial organs (FIG. 4C; Table 1). One gene, Gr2B1, isexpressed solely in the labral sense organ and is not detected in theproboscis labellum or in the cibarial organs (FIG. 4D).

[0317] Chemosensory bristles also decorate both the legs and wings ofDrosophila with about 40 chemosensory hairs on each structure (Nayak andSingh, 1983; Hartenstein and Posakony, 1989). One gene, Gr32D1,expressed both in the proboscis and cibarial organ, is also expressed intwo to three neurons in the most distal tarsal segments of all legs(FIG. 4E). These results are consistent with the observation thatexposure of the legs to tastants results in proboscis extension andfeeding behavior (Dethier, 1976). The observation that members of thisgene family are expressed in the proboscis and in chemosensory cells ofthe internal mouth organs and leg suggests that this gene family encodesgustatory receptors.

[0318] Expression of Gustatory Receptors in Drosophila Larvae

[0319] The expression of GR transgenes in larvae was also examined. Thedetection of food in larvae is mediated by chemosensors that residelargely in the antennal-maxillary complex, a bilaterally symmetricanterior structure composed of the dorsal and terminal organs (FIG. 5A;Table 1) (Stocker, 1994; Campos-Ortega and Hartenstein, 1997; Heimbecket al., 1999). Each of the two larval chemosensory organs comprisesabout 40 neurons. Neurons of the dorsal organ primarily detect volatileodorants (Stocker, 1994), whereas the terminal organ is thought todetect both soluble and volatile chemical cues (Heimbeck et al., 1999).

[0320] The possiblity that members of the GR family are expressed inlarval chemosensory cells was addressed by examining the larval progenythat result from crosses between GR promoter-Gal4 and UAS-GFP flies.Examination of live larvae by direct fluorescent microscopy reveals thatfive of the seven GRs expressed in the adult are expressed in singleneurons within the terminal organ (FIG. 5 and Table 1). GR-promoterfusions from each of the 5 genes show bilateral expression of GFP bothin the neuronal cell body and in the dendrite. The dendrites extendanteriorly to terminate in the terminal organ, a dome-shaped structurethat opens to the environment. In about 5% of the larvae, a secondpositive cell is observed in each of the lines.

[0321] Gr2B1 is expressed in only a single neuron in the labral senseorgan of the adult, but is expressed in an extensive population ofchemosensory cells in larvae. This gene is expressed in two neuronsinnervating the dorsal organ, one neuron innervating the terminal organ,and a single bilaterally symmetric neuron innervating the ventral pit ineach thoracic hemisegment (FIG. 5C). The ventral pit contains a singlesensory neuron that may be involved in contact chemosensation. The GRgenes are therefore likely to play a significant role in chemosensoryrecognition in larvae as well as adults.

[0322] The Diversity of GR Expression in Individual Neurons

[0323] Olfactory neurons of mammals as well as Drosophila express asingle odorant receptor such that the brain can discriminate odor bydetermining which neurons have been activated (Ngai et al., 1993;Ressler et al., 1993; Vassar et al., 1993; Chess et al., 1994; Gao etal., 2000; Vosshall et al., 2000). In contrast, nematode olfactoryneurons and mammalian gustatory cells co-express multiple receptor genes(Bargmann and Horvitz, 1991; Troemel et al., 1995; Hoon et al., 1999;Adler et al., 2000). The diversity of GR gene expression in individuallarval taste neurons was therefore examined. In larvae, most receptorsare expressed in only one neuron in the terminal organ. Crosses betweenfive GR promoter-Gal4 lines and flies bearing UAS-GFP reveal a singleintensely stained neuron within each terminal organ. Seven lines bearingtwo different GR promoter-Gal4 transgenes along with the UAS-GFPreporter were then generated. In every line bearing two GR promoter-Gal4fusions, two GFP positive cells per terminal organ were observed (FIG.5F, 5G). These experiments demonstrate that individual gustatory neuronsof larvae express different complements of receptors and are likely torespond to different chemosensory cues.

[0324] The Projections of Larval Chemosensory Neurons to the Brain

[0325] In other sensory systems, a spatial map of receptor activation inthe periphery is maintained in the brain such that the quality of asensory stimulus may be encoded in spatially defined patterns of neuralactivity. GR promoter-Gal4 transgenes were therefore used to drive theexpression of UAS-nSyb-GFP to visualize the projections of sensoryneurons expressing different GR genes. nSyb-GFP is a C-terminal fusionof green fluorescent protein to neuronal synaptobrevin that selectivelylabels synaptic vesicles, allowing the visualization of terminal axonalprojections (Estes et al., 2000). Whole mount brain preparations fromtransgenic flies were examined by immunofluorescence with an antibodyagainst GFP and a monoclonal antibody, nc82, which labels neuropil andidentifies the individual glomeruli in the antennal lobe (Laissue etal., 1999). These experiments were initially performed with larvaebecause of the relative simplicity of the larval brain and theobservation that a given GR is expressed in only a small number ofgustatory neurons.

[0326] The Drosophila larval brain is composed of two dorsal brainhemispheres fused to the ventral hindbrain (FIG. 6A). The brainhemispheres and the hindbrain contain an outer shell of neuronal cellbodies and a central fibrous neuropil. Determination of the number ofneuroblasts and the number of cell divisions suggest that there areapproximately 10,000-15,000 neurons in the larval brain, a value 10-20fold lower than in the adult (Hartenstein and Campos-Ortega, 1984;Hartenstein et al., 1987; Truman et al., 1993). Chemosensory neuronssend axonal projections to two distinct regions of the larval brain, theantennal lobe and the subesophageal ganglion (SOG) (Stocker, 1994;Heimbeck, et al., 1999). The antennal lobe is a small neuropil in themedial aspect of the deuterocerebrum within each brain hemisphere. Theantennal lobe receives input from neurons of the dorsal and terminalorgan and presumably participates in processing olfactory information.The SOG resides in the most anterior aspect of the hindbrain, at thejuncture of the hindbrain with the brain hemispheres. The SOG receivesinput from the terminal organ and mouthparts and is thought to processgustatory information. Whereas the projections of populations ofchemosensory cells have been traced to the antennal lobe and the SOG,the patterns of axonal projections for individual sensory cells have notbeen described. Moreover, the connections of chemosensory axons withsecond order brain neurons is unknown for the larval brain.

[0327] Gr32D1-Gal4 is expressed in multiple neurons in the proboscis ofthe adult, but it is expressed in only a single neuron in the terminalorgan of larvae (FIG. 5B). In larvae containing the Gr32D1-Gal4 andUAS-nSyb-GFP transgenes, it is possible to visualize the axons of Gr32D1expressing cells as they course posteriorly to enter the subesophagealganglion (data not shown). The axons then turn dorsally and intenselystained fibers terminate in the medial aspect of the SOG (FIG. 6C). Asimilar pattern is observed for neurons expressing Gr66C1 (FIG. 6B, D),a gene expressed in the proboscis in the adult and in a single neuron inthe terminal organ and two in the mouth of larvae (FIG. 5E). However,the terminal arbors of Gr66C1 neurons are consistently thicker than thatobserved for Gr32D1, perhaps reflecting the increased number ofGr66C1-bearing neurons. The reporter nSyb-GFP stains axons only weaklybut shows intense staining of what is likely to be terminal projectionsof sensory neurons that synapse on second order neurons in the neuropilof the SOG. This terminal arbor extends for about 40 um and reveals alooser, more distributed pattern that the tight neuropil of theolfactory glomerulus. The position and pattern of the terminalprojections from individual chemosensory cells in the terminal organshow bilateral symmetry and are maintained in over 20 larvae examined.

[0328] A more complex pattern of projections is observed for Gr2B1, agene expressed in one neuron in the terminal organ, two in the dorsalorgan, and a single bilaterally symmetric neuron in each thoracichemisegment (FIG. 5C). One set of fibers appears to terminate in theantennal lobe (FIG. 6E). A second more posterior set of fibers can betraced from the thorax into the hindbrain, with fibers terminatingposterior to the antennal lobe (FIG. 6E). This pattern of projections isof interest for it implies that neurons in different locations in larvaethat express the same receptor project to discrete locations in thelarval brain, suggesting the possibility that the same chemosensorystimulus can elicit distinct behavioral outputs.

[0329] An attempt was made to determine whether neurons in the terminalorgan that express different GRs project to discrete loci within theSOG. Larvae that express two promoter fusions, Gr66C1-Gal4 andGr32D1-Gal4, along with a UAS-nSyb-GFP transgene were generated. Theprojections in these flies are broadened, suggesting that these sets ofneurons terminate in overlapping but non-identical regions of the SOG(FIG. 6F). More definitive data to support the existence of atopographic map of taste quality will require two color labelling of thedifferent fibers to discern whether the projections from neuronsexpressing different GRs are spatially segregated in the SOG.

[0330] Are GRs Also Odorant Receptors?

[0331] A large family of presumed olfactory receptor genes in Drosophila(the DOR genes) has been identified that is distinct from the GR genefamily (Clyne et al., 1999; Gao and Chess, 1999; Vosshall et al., 1999;Vosshall et al., 2000). Expression of the DOR genes is only observed inolfactory sensory neurons within the antenna and maxillary palp, where agiven DOR gene is expressed in a spatially invariant subpopulation ofcells (Clyne et al., 1999; Gao and Chess, 1999; Vosshall et al., 1999;Vosshall et al., 2000). In situ hybridization experiments demonstratethat three members of the GR gene family are also expressed insubpopulations of antennal neurons (FIG. 2B). These observations suggesteither that the odorant receptors in Drosophila are encoded by at leasttwo different gene families or that previously unidentified tasteresponsive neurons reside within the antenna.

[0332] In Drosophila, olfactory information is transmitted to theantennal lobe, whereas gustatory neurons in the proboscis and mouthrelay sensory information to the subesophageal ganglion (Stocker, 1994).The spatial pattern of expression of GRs in the antenna and the patternof projections of their sensory axons in the brain were thereforeexamined. In situ hybridization with the three GR genes reveals thateach gene is expressed in about 20-30 cells/gene in the antenna (FIG.2B). Similar results are obtained in a cross between an antennal GRpromoter-Gal4 line, Gr2D1-Gal4, and UAS-LacZ or UAS-GFP lines (FIG. 7A,7B). This pattern of GR gene expression is maintained in over 50antennae that have been analyzed. The GR-positive cells occupy regionsof the antenna that do not express identified members of the DOR genefamily (Vosshall et al., 2000), suggesting that there is spatialseggregation of these two receptor families.

[0333] Whether antennal neurons expressing a GR gene project to theantennal lobe in a manner analogous to that observed for cellsexpressing the DOR genes was next addressed. Transgenic flies expressinga Gr21D1 promoter-Gal4 fusion were crossed to animals bearing theUAS-nSyb-GFP transgene. These studies demonstrate that neuronsexpressing the Gr2D1 transgene project to a single, bilaterallysymmetric glomerulus in the ventral-most region of the antennal lobe(the V glomerulus) (FIG. 7C) (Stocker et al., 1990; Laissue et al.,1999) and do not project to the SOG. Thus, as in the case of the familyof DOR genes (Gao et al., 2000; Vosshall et al., 2000), neuronsexpressing the same receptor project to a single spatially invariantglomerulus.

[0334] Gr21D1 is also expressed in one cell of the terminal organ oflarvae (FIG. 5D). The projections of Gr2D1-bearing neurons weretherefore traced to the larval brain. Gr21D1 axons enter the larvalbrain and terminate in the antennal lobe rather than the SOG (FIG. 6G).The segregation of projections from presumed olfactory and gustatoryneurons is apparent in larvae that contain Gr2D1-Gal4 and Gr66C1-Gal4along with UAS-nSyb-GFP. In these transgenic flies, two distinct sets oftermini are observed, one entering the SOG, and a second entering theantennal lobe (FIG. 6H).

[0335] Thus, a member of the GR gene family is expressed in sensoryneurons of the antenna and the terminal organ of larvae, and GR-bearingneurons project to the antennal lobe. These data indicate that at leasttwo independent gene families, the DORs and the GRs, recognize olfactoryinformation. The GR gene family is therefore likely to encode botholfactory and gustatory receptors, and neurons expressing distinctclasses of GR receptors project to different regions of the fly brain.

[0336] Table 1. Summary of Drosophila Chemosensory Tissues and GRTransgene Expression Patterns.

[0337] The table summarizes the expression patterns of GR promoter-Gal4transgenes in adult and larval chemosensory tissues. Adult Drosophilasense gustatory cues with chemosensory bristles on the labellum of theproboscis, legs and wings, and with specialized structures of theinternal mouthparts, the cibarial organs and the labral sense organ.Gustatory neurons on the proboscis send axonal projections to thesubesophageal ganglion (SOG). Sensory neurons on the antenna recognizeolfactory cues and project to the antennal lobe (AL). In Drosophilalarvae, gustatory cues are recognized by neurons innervating theterminal organ and possibly the ventral pits, and olfactory cues arerecognized by neurons innervating the dorsal organ and the terminalorgan. Gustatory tissues are highlighted in blue and olfactory tissuesare highlighted in pink. The schematic of the adult fly is adapted fromStocker (1994). The schematic of the larva is adapted from Struhl(1981). TABLE 1 Expression profiles of GR transgenes ADULT LARVA In situcibarial labral terminal dorsal ventral GR signal labellum antennaorgans organ leg organ organ mouth gut pits Gr2B1 — − − − + − + + − + +Gr21D1 antenna − + − − − + − − − − Gr22B1 — + − − − − − − − − − Gr28A1labellum + − + − − + − + − − Gr32D1 labellum + − + − + + − − − − Gr47A1labellum + − − − − − − − − − Gr66C1 labellum + − + − − + − + − −

[0338] Discussion

[0339] A Family of Gustatory and Olfactory Receptors

[0340] Specialized sense organs have evolved to recognize chemosensoryinformation in the environment. The antennae in insects, the amphid innematodes, and the nose of mammals allow the recognition of a vastrepertoire of volatile odorants often over long distances. Taste organshave evolved to accommodate a distinct function, the recognition ofsoluble chemical cues over shorter distances. In vertebrates, taste islargely restricted to the tongue and palate, whereas in insects,gustatory neurons are more broadly distributed along the body plan andreside not only in the proboscis and pharynx but also on the wings,legs, and female genitalia. Anatomic and functional segregation of thegustatory and olfactory systems is not only apparent in the peripheralreceptor field but in the projections to the brain. In the fly, forexample, olfactory neurons project to the antennal lobe, whereas mostgustatory neurons ultimately synapse within the subesophageal ganglion.This separation is also observed in vertebrates where taste and smellare accommodated by distinct sense organs and conveyed to differentbrain regions by different cranial nerves. Thus, a common sensoryfunction, the recognition of chemical cues, has undergone specializationto allow for the recognition of at least two distinct categories ofchemosensory information, each eliciting distinct behavioral responses.

[0341] This study has characterized the patterns of expression of alarge family of genes in Drosophila that are likely to encode bothodorant and gustatory receptors. A family of candidate taste receptorswas identified by searching the Drosophila genome with an algorithmdesigned to detect genes encoding seven transmembrane domain proteins(Clyne et al., 2000). This analysis was extended through a search of thecomplete euchromatic genome of Drosophila and identify 56 genes withinthe family. All of the GR genes contain a signature motif in thecarboxyl terminus that is also present within some members of the DORgene family, suggesting that these two families share a common origin.

[0342] The GR family of proteins was tentatively identified as gustatoryreceptors solely on the basis of PCR analysis of proboscis RNA (Clyne etal., 2000). In situ hybridization and transgene experiments demonstratethat members of this gene family are expressed in the antennae,proboscis, pharynx, leg, and larval chemosensory organs. Thus, a singlegene family encodes chemosensory receptors containing both olfactory andgustatory receptors. Flies bearing GR promoter transgenes were generatedfrom 15 GR genes. Expression is observed in seven lines and isrestricted to chemosensory cells. No expression is detected in otherneurons or in non-neuronal cells. These data suggest that the expressionof this family is limited to gustatory and olfactory neurons, and thatthe inability to observe expression in 8 transgenic lines perhapsreflects the structural inadequacy of the promoters.

[0343] A common gene family encoding both olfactory and taste receptorsis not present in vertebrates where the main olfactory epithelium, thevomeronasal organ and the tongue express receptors encoded byindependent gene families (Buck and Axel, 1991; Dulac and Axel, 1995;Herrada and Dulac, 1997; Matsunami and Buck, 1997; Ryba and Tirindelli,1997; Hoon et al., 1999; Adler et al., 2000; Matsunami et al., 2000).The observations described herein are more reminiscent of thechemosensory receptor families in C. elegans that encode odorantreceptors expressed in the amphid neurons and taste receptors in sensoryneurons responsive to soluble chemicals (Troemel et al., 1995; Troemel,1999).

[0344] Patterns of GR Gene Expression and Taste Modalities

[0345] The size of the family of candidate taste receptors and thepattern of expression in chemosensory cells provides insight into theproblem of the recognition and discrimination of gustatory cues. Onaverage, each GR is expressed in 5% of the cells in the proboscislabellum, suggesting that the proboscis alone will contain at least 20distinct taste cells expressing about 20 different GR receptors.Moreover, a given receptor is expressed in one of the four rows ofsensilla such that the sensilla in different rows are likely to befunctionally distinct. Electrophysiologic studies have suggested thatall sensilla are identical and contain four distinct cells eachresponsive to a different category of taste (Dethier, 1976; Rodriquesand Siddiqi, 1978; Fujishiro et al., 1984). The data presented hereinare not consistent with these conclusions and argue that different rowsof sensilla are likely to contain cells with different tastespecificities.

[0346] At present the nature of the ligands recognized by these GRreceptors are not known, nor is it known whether all taste modalitiesare recognized by this gene family. In mammals, gustatory cues haveclassically been grouped into five categories: sweet, bitter, salt, sourand glutamate (umami) (Kinnamon and Margolskee, 1996; Lindemann, 1996;Gilbertson et al., 2000). Sugar and bitter taste are likely to bemediated by G protein-coupled receptors since these modalities requirethe function of a taste cell-specific G_(a) subunit, gustducin(McLaughlin et al., 1992; Wong et al., 1996). Recently, two novelfamilies of seven transmembrane proteins (the TlRs and T2Rs) were shownto be selectively expressed in taste cells in the tongue and palateepithelium (Hoon et al., 1999; Adler et al., 2000; Matsunami et al.,2000). Genetic experiments implicated members of the T2R family in therecognition of bitter tastants (Adler et al., 2000; Matsunami et al.,2000) and functional studies directly demonstrated that members of theT2R family serve as gustducin-linked bitter taste receptors.(Chandrashekar et al., 2000). A large number of candidate genes havebeen suggested to encode receptors for other taste modalities but inonly a few instances have functional data and expression patternssupported these assumptions. In mammals, an amiloride-sensitive sodiumchannel has been suggested as the salt receptor (Heck et al., 1984), adegenerin homolog (MDEG-1) (Ugawa et al., 1998) and a potassium channel(Kinnamon et al., 1988) as sour or pH sensors, and a rare splice form ofthe metabotropic glutamate receptor as the umami sensor (Chaudhari etal., 2000). In Drosophila, genetic analysis of mutant flies defective inthe recognition of the sugar, trehalose, has led to the identificationof a transmembrane receptor distinct from GRs that reduces thesensitivity to one class of sugars (Ishimoto et al., 2000). Theinterpretation of the role of these putative taste receptors in tasteperception awaits a more definitive association between tastant and geneproduct.

[0347] The Logic of Taste Discrimination

[0348] How does the fly discriminate among multiple tastants? Onemechanism of chemosensory discrimination, thought to operate in theolfactory system of insects and vertebrates, requires that individualsensory neurons express only one of multiple receptor genes (Buck andAxel, 1991; Ngai et al., 1993; Ressler et al., 1993; Vassar et al.,1993; Chess et al., 1994; Clyne et al., 1999; Gao and Chess, 1999;Vosshall et al., 1999). Neurons expressing a given receptor projectaxons that converge on topographically invariant glomeruli such thatdifferent odors elicit different patterns of spatial activity in thebrain (Ressler et al., 1994; Vassar et al., 1994; Mombaerts et al.,1996; Wang et al., 1998; Gao et al., 2000; Vosshall et al., 2000). Thenematode C. elegans uses a rather different logic, in which a givensensory neuron dictates a specific behavior but expresses multiplereceptors (Bargmann and Horvitz, 1991; Troemel et al., 1995; Troemel etal., 1997). In the worm olfactory system, discrimination is necessarilymore limited and exploits mechanisms to diversify the limited number ofsensory cells (Colbert and Bargmann, 1995; Troemel et al., 1999;L'Etoile and Bargmann, 2000). A similar logic has been suggested formammalian taste. Several members of the T2R family of about 50 receptorgenes, each thought to encode bitter sensors, are co-expressed insensory cells within the tongue (Adler et al., 2000). This organizationallows the organism to recognize a diverse repertoire of aversivetastants but limits the ability to discriminate among them.

[0349] What can be discerned about the logic of taste discriminationfrom the pattern of GR gene expression in Drosophila? First, the numberof GR genes, 56, approximates the number of DOR genes, suggesting thatthe fly recognizes diverse repertoires of both soluble and volatilechemical cues. Moreover, the data presented herein argue that individualsensory neurons differ with respect to receptor gene expression and aretherefore functionally distinct. Experiments with Drosophila larvaedemonstrate that a given GR gene is expressed in one neuron in thelarval terminal organ. Strains bearing two different GR-promoter fusionsreveal twice the number of expressing cells. Similar results areobtained in adult gustatory organs (data not shown). More definitiveexperiments to examine the diversity of receptor expression in a singleneuron, employed successfully in the olfactory system, have beendifficult since the levels of GR RNA are 10-20 fold lower than odorantreceptor RNA levels. Nevertheless, experiments described hereindemonstrate that different gustatory neurons express differentcomplements of GR genes and at the extreme are consistent with a modelin which gustatory neurons express only a single receptor gene.

[0350] How does the brain discern which of the different gustatoryneurons is activated by a given tastant? As in other sensory systems, itis possible that axons from different taste neurons segregate tospatially distinct loci in the subesophageal ganglion. In such a model,taste quality would be represented by different spatial patterns ofactivity in the brain. Preliminary experiments suggest that neuronsexpressing different GRs project to spatially segregated loci within thebrain. Clear segregation of axonal termini is observed for presumedtaste neurons that project to the SOG and olfactory neurons that projectto the antennal lobe. A second interesting pattern of projections isobserved for the presumed gustatory receptor Gr2B1, a gene expressed inneurons in the terminal and dorsal organs and in a single neuron in theventral pit present bilaterally in each thoracic segment. At least twospatially segregated targets are observed for these neurons in thelarval brain: one set of fibers terminates in glomeruli of the antennallobe and a second set of fibers (from the ventral pits) project to theSOG. Thus, neurons expressing the same receptor in differentchemosensory organs project to distinct brain regions. In this manner,the same chemosensory cue could elicit distinct behaviors depending uponthe cell it activates. Sucrose, for example, could ellicitchemoattraction upon exposure to the thoracic neurons and eatingbehavior upon activation of neurons in the terminal and dorsal organ.

[0351] These data establish that presumed olfactory neurons andgustatory neurons expressing GR genes project to different regions ofthe larval brain. Taste neurons expressing different GR genes, however,all project to the SOG. The current data do not permit us to discernwhether axons from neurons expressing different GR genes project tospatially distinct loci within the SOG. The axon termini of gustatoryneurons terminate in more diffuse, elongated structures than the tightlycompacted glomeruli formed by olfactory sensory axons, rendering itdiffcult at present to discern a topographic map of gustatoryprojections in the larval brain.

[0352] Sensory Perception in Larvae

[0353] Insects provide an attractive model system for the study ofchemosensory perception because they exhibit sophisticated taste andolfactory driven behaviors that are controlled by a chemosensory systemthat is anatomically and genetically simpler than vertebrates (Nassif etal., 1998). Drosophila larvae afford a particularly facile organismbecause much of their behavior surrounds eating. Gustatory neurons inthe terminal organ and along the body plan, together with olfactorysensory cells in the dorsal and terminal organs, combine to identifyfood sources and elicit eating behaviors (Stocker, 1994).

[0354] Members of the Drosophila odorant receptor (DOR) family areexpressed in the adult olfactory system but cannot be detected in larvalchemosensory organs. GR genes are expressed in larval olfactory andgustatory neurons and may encode the entire repertoire of larvalchemosensory receptors. The simplicity of the Drosophila larvae, coupledwith the ease of behavioral studies, suggests that it may be possible torelate the recognition of chemosensory information to specificbehavioral responses and ultimately to associate changes in behaviorwith modifications in specific connections.

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1 116 1 410 PRT Drosophila melanogaster 1 Met Asp Thr Leu Arg Ala LeuGlu Pro Leu His Arg Ala Cys Gln Val 1 5 10 15 Cys Asn Leu Trp Pro TrpArg Leu Ala Pro Pro Pro Asp Ser Glu Gly 20 25 30 Ile Leu Leu Arg Arg SerArg Trp Leu Glu Leu Tyr Gly Trp Thr Val 35 40 45 Leu Ile Ala Ala Thr SerPhe Thr Val Tyr Gly Leu Phe Gln Glu Ser 50 55 60 Ser Val Glu Glu Lys GlnAsp Ser Glu Ser Thr Ile Ser Ser Ile Gly 65 70 75 80 His Thr Val Asp PheIle Gln Leu Val Gly Met Arg Val Ala His Leu 85 90 95 Ala Ala Leu Leu GluAla Leu Trp Gln Arg Gln Ala Gln Arg Gly Phe 100 105 110 Phe Ala Glu LeuGly Glu Ile Asp Arg Leu Leu Ser Lys Ala Leu Arg 115 120 125 Val Asp ValGlu Ala Met Arg Ile Asn Met Arg Arg Gln Thr Ser Arg 130 135 140 Arg AlaVal Trp Ile Leu Trp Gly Tyr Ala Val Ser Gln Leu Leu Ile 145 150 155 160Leu Gly Ala Lys Leu Leu Ser Arg Gly Asp Arg Phe Pro Ile Tyr Trp 165 170175 Ile Ser Tyr Leu Leu Pro Leu Leu Val Cys Gly Leu Arg Tyr Phe Gln 180185 190 Ile Phe Asn Ala Thr Gln Leu Val Arg Gln Arg Leu Asp Val Leu Leu195 200 205 Val Ala Leu Gln Gln Leu Gln Leu His Gln Lys Gly Pro Ala ValAsp 210 215 220 Thr Val Leu Glu Glu Gln Glu Asp Leu Glu Glu Ala Ala MetAsp Arg 225 230 235 240 Leu Ile Ala Val Arg Leu Val Tyr Gln Arg Val TrpAla Leu Val Ala 245 250 255 Leu Leu Asn Arg Cys Tyr Gly Leu Ser Met LeuMet Gln Val Gly Asn 260 265 270 Asp Phe Leu Ala Ile Thr Ser Asn Cys TyrTrp Met Phe Leu Asn Phe 275 280 285 Arg Gln Ser Ala Ala Ser Pro Phe AspIle Leu Gln Ile Val Ala Ser 290 295 300 Gly Val Trp Ser Ala Pro His LeuGly Asn Val Leu Val Leu Ser Leu 305 310 315 320 Leu Cys Asp Arg Thr AlaGln Cys Ala Ser Arg Leu Ala Leu Cys Leu 325 330 335 His Gln Val Ser ValAsp Leu Arg Asn Glu Ser His Asn Ala Leu Ile 340 345 350 Thr Gln Phe SerLeu Gln Leu Leu His Gln Arg Leu His Phe Ser Ala 355 360 365 Ala Gly PhePhe Asn Val Asp Cys Thr Leu Leu Tyr Thr Ile Val Gly 370 375 380 Ala ThrThr Thr Tyr Leu Ile Ile Leu Ile Gln Phe His Met Ser Glu 385 390 395 400Ser Thr Ile Gly Ser Asp Ser Asn Gly Gln 405 410 2 385 PRT Drosophilamelanogaster 2 Met Ser Gly His Leu Gly Arg Val Leu Gln Phe His Leu ArgLeu Tyr 1 5 10 15 Gln Val Leu Gly Phe His Gly Leu Pro Leu Pro Gly AspGly Asn Pro 20 25 30 Ala Arg Thr Arg Arg Arg Leu Met Ala Trp Ser Leu PheLeu Leu Ile 35 40 45 Ser Leu Ser Ala Leu Val Leu Ala Cys Leu Phe Ser GlyGlu Glu Phe 50 55 60 Leu Tyr Arg Gly Asp Met Phe Gly Cys Ala Asn Asp AlaLeu Lys Tyr 65 70 75 80 Val Phe Ala Glu Leu Gly Val Leu Ala Ile Tyr LeuGlu Thr Leu Ser 85 90 95 Ser Gln Arg His Leu Ala Asn Phe Trp Trp Leu HisPhe Lys Leu Gly 100 105 110 Gly Gln Lys Thr Gly Leu Val Ser Leu Arg SerGlu Phe Gln Gln Phe 115 120 125 Cys Arg Tyr Leu Ile Phe Leu Tyr Ala MetMet Ala Ala Glu Val Ala 130 135 140 Ile His Leu Gly Leu Trp Gln Phe GlnAla Leu Thr Gln His Met Leu 145 150 155 160 Leu Phe Trp Ser Thr Tyr GluPro Leu Val Trp Leu Thr Tyr Leu Arg 165 170 175 Asn Leu Gln Phe Val LeuHis Leu Glu Leu Leu Arg Glu Gln Leu Thr 180 185 190 Gly Leu Glu Arg GluMet Gly Leu Leu Ala Glu Tyr Ser Arg Phe Ala 195 200 205 Ser Glu Thr GlyArg Ser Phe Pro Gly Phe Glu Ser Phe Leu Arg Arg 210 215 220 Arg Leu ValGln Lys Gln Arg Ile Tyr Ser His Val Tyr Asp Met Leu 225 230 235 240 LysCys Phe Gln Gly Ala Phe Asn Phe Ser Ile Leu Ala Val Leu Leu 245 250 255Thr Ile Asn Ile Arg Ile Ala Val Asp Cys Tyr Phe Met Tyr Tyr Ser 260 265270 Ile Tyr Asn Asn Val Ile Asn Asn Asp Tyr Tyr Leu Ile Val Pro Ala 275280 285 Leu Leu Glu Ile Pro Ala Phe Ile Tyr Ala Ser Gln Ser Cys Met Val290 295 300 Val Val Pro Arg Ile Ala His Gln Leu His Asn Ile Val Thr AspSer 305 310 315 320 Gly Cys Cys Ser Cys Pro Asp Leu Ser Leu Gln Ile GlnAsn Phe Ser 325 330 335 Leu Gln Leu Leu His Gln Pro Ile Arg Ile Asp CysLeu Gly Leu Thr 340 345 350 Ile Leu Asp Cys Ser Leu Leu Thr Arg Met AlaCys Ser Val Gly Thr 355 360 365 Tyr Met Ile Tyr Ser Ile Gln Phe Ile ProLys Phe Ser Asn Thr Tyr 370 375 380 Met 385 3 381 PRT Drosophilamelanogaster 3 Met Gln Arg Thr His Leu Glu Phe Glu Phe Lys Asn Ala ProGln Glu 1 5 10 15 Pro Lys Arg Pro Phe Glu Phe Phe Met Tyr Phe Lys PheCys Leu Ile 20 25 30 Asn Leu Met Met Met Ile Gln Val Cys Gly Ile Phe AlaGln Tyr Gly 35 40 45 Glu Val Gly Lys Gly Ser Val Ser Gln Val Arg Val HisPhe Ala Ile 50 55 60 Tyr Ala Phe Val Leu Trp Asn Tyr Thr Glu Asn Met AlaAsp Tyr Cys 65 70 75 80 Tyr Phe Ile Asn Gly Ser Val Leu Lys Tyr Tyr ArgGln Phe Asn Leu 85 90 95 Gln Leu Gly Ser Leu Arg Asp Glu Met Asp Gly LeuArg Pro Gly Gly 100 105 110 Met Leu Leu His His Cys Cys Glu Leu Ser AspArg Leu Glu Glu Leu 115 120 125 Arg Arg Arg Cys Arg Glu Ile His Asp LeuGln Arg Glu Ser Phe Arg 130 135 140 Met His Gln Phe Gln Leu Ile Gly LeuMet Leu Ser Thr Leu Ile Asn 145 150 155 160 Asn Leu Thr Asn Phe Tyr ThrLeu Phe His Met Leu Ala Lys Gln Ser 165 170 175 Leu Glu Glu Val Ser TyrPro Val Val Val Gly Ser Val Tyr Ala Thr 180 185 190 Gly Phe Tyr Ile AspThr Tyr Ile Val Ala Leu Ile Asn Glu His Ile 195 200 205 Lys Leu Glu LeuGlu Ala Val Ala Leu Thr Met Arg Arg Phe Ala Glu 210 215 220 Pro Arg GluMet Asp Glu Arg Leu Thr Arg Glu Val Arg Asn Lys Ile 225 230 235 240 PheSer Phe Leu Ala Thr Thr Leu Glu Ile Met Ile Gln Ile Trp Leu 245 250 255Ser Phe Phe Ala Asn Phe Asp Asp Val Thr Pro Tyr Arg Lys Cys Glu 260 265270 Asn Arg Pro Lys Asn Leu Phe Phe Lys Ile Arg Gln Lys Val Ile Gly 275280 285 Ile Val Ser Ser Gly Lys Leu Lys Leu Leu Val Ser Leu Arg Phe Phe290 295 300 Ile Ile Asp Asn Arg Leu Ile Leu Asn Leu His Lys Tyr Leu AlaIle 305 310 315 320 Lys Leu Asn Phe Leu Asn Leu Ile Gln Ile Glu His LeuSer Leu Glu 325 330 335 Leu Leu Asn Tyr Gln Pro Pro Met Leu Cys Gly LeuLeu His Leu Asp 340 345 350 Arg Arg Leu Val Tyr Leu Ile Ala Val Thr AlaPhe Ser Tyr Phe Ile 355 360 365 Thr Leu Val Gln Phe Asp Leu Tyr Leu ArgLys Lys Ser 370 375 380 4 373 PRT Drosophila melanogaster 4 Met Arg ValGly Lys Leu Cys Arg Leu Ala Leu Arg Phe Trp Met Gly 1 5 10 15 Leu IleLeu Val Leu Gly Phe Ser Ser His Tyr Tyr Asn Pro Thr Arg 20 25 30 Arg ArgLeu Val Tyr Ser Arg Ile Leu Gln Thr Tyr Asp Trp Leu Leu 35 40 45 Met ValIle Asn Leu Gly Ala Phe Tyr Leu Tyr Tyr Arg Tyr Ala Met 50 55 60 Thr TyrPhe Leu Glu Gly Met Phe Arg Arg Gln Gly Phe Val Asn Gln 65 70 75 80 ValSer Thr Cys Asn Val Phe Gln Gln Leu Leu Met Ala Val Thr Gly 85 90 95 ThrTrp Leu His Phe Leu Phe Glu Arg His Val Cys Gln Thr Tyr Asn 100 105 110Glu Leu Ser Arg Ile Leu Lys His Asp Leu Lys Leu Lys Glu His Ser 115 120125 Arg Phe Tyr Cys Leu Ala Phe Leu Ala Lys Val Tyr Asn Phe Phe His 130135 140 Asn Phe Asn Phe Ala Leu Ser Ala Ile Met His Trp Gly Leu Arg Pro145 150 155 160 Phe Asn Val Trp Asp Leu Leu Ala Asn Leu Tyr Phe Val TyrAsn Ser 165 170 175 Leu Ala Arg Asp Ala Ile Leu Val Ala Tyr Val Leu LeuLeu Leu Asn 180 185 190 Leu Ser Glu Ala Leu Arg Leu Asn Gly Gln Gln GluHis Asp Thr Tyr 195 200 205 Ser Asp Leu Met Lys Gln Leu Arg Arg Arg GluArg Leu Leu Arg Ile 210 215 220 Gly Arg Arg Val His Arg Met Phe Ala TrpLeu Val Ala Ile Ala Leu 225 230 235 240 Ile Tyr Leu Val Phe Phe Asn ThrAla Thr Ile Tyr Leu Gly Tyr Thr 245 250 255 Met Phe Ile Gln Lys His AspAla Leu Gly Leu Arg Gly Arg Gly Leu 260 265 270 Lys Met Leu Leu Thr ValVal Ser Phe Leu Val Ile Leu Trp Asp Val 275 280 285 Val Leu Leu Gln ValIle Cys Glu Lys Leu Leu Ala Glu Glu Asn Lys 290 295 300 Ile Cys Asp CysPro Glu Asp Val Ala Ser Ser Arg Thr Thr Tyr Arg 305 310 315 320 Gln TrpGlu Met Ser Ala Leu Arg Arg Ala Ile Thr Arg Ser Ser Pro 325 330 335 GluAsn Asn Val Leu Gly Met Phe Arg Met Asp Met Arg Cys Ala Phe 340 345 350Ala Leu Ile Ser Cys Ser Leu Ser Tyr Gly Ile Ile Ile Ile Gln Ile 355 360365 Gly Tyr Ile Pro Gly 370 5 431 PRT Drosophila melanogaster 5 Met AlaPhe Lys Leu Trp Glu Arg Phe Ser Gln Ala Asp Asn Val Phe 1 5 10 15 GlnAla Leu Arg Pro Leu Thr Phe Ile Ser Leu Leu Gly Leu Ala Pro 20 25 30 PheArg Leu Asn Leu Asn Pro Arg Lys Glu Val Gln Thr Ser Lys Phe 35 40 45 SerPhe Phe Ala Gly Ile Val His Phe Leu Phe Phe Val Leu Cys Phe 50 55 60 GlyIle Ser Val Lys Glu Gly Asp Ser Ile Ile Gly Tyr Phe Phe Gln 65 70 75 80Thr Asn Ile Thr Arg Phe Ser Asp Gly Thr Leu Arg Leu Thr Gly Ile 85 90 95Leu Ala Met Ser Thr Ile Phe Gly Phe Ala Met Phe Lys Arg Gln Arg 100 105110 Leu Val Ser Ile Ile Gln Asn Asn Ile Val Val Asp Glu Ile Phe Val 115120 125 Arg Leu Gly Met Lys Leu Asp Tyr Arg Arg Ile Leu Leu Ser Ser Phe130 135 140 Leu Ile Ser Leu Gly Met Leu Leu Phe Asn Val Ile Tyr Leu CysVal 145 150 155 160 Ser Tyr Ser Leu Leu Val Ser Ala Thr Ile Ser Pro SerPhe Val Thr 165 170 175 Phe Thr Thr Phe Ala Leu Pro His Ile Asn Ile SerLeu Met Val Phe 180 185 190 Lys Phe Leu Cys Thr Thr Asp Leu Ala Arg SerArg Phe Ser Met Leu 195 200 205 Asn Glu Ile Leu Gln Asp Ile Leu Asp AlaHis Ile Glu Gln Leu Ser 210 215 220 Ala Leu Glu Leu Ser Pro Met His SerVal Val Asn His Arg Arg Tyr 225 230 235 240 Ser His Arg Leu Arg Asn LeuIle Ser Thr Pro Met Lys Arg Tyr Ser 245 250 255 Val Thr Ser Val Ile ArgLeu Asn Pro Glu Tyr Ala Ile Lys Gln Val 260 265 270 Ser Asn Ile His AsnLeu Leu Cys Asp Ile Cys Gln Thr Ile Glu Glu 275 280 285 Tyr Phe Thr TyrPro Leu Leu Gly Ile Ile Ala Ile Ser Phe Leu Phe 290 295 300 Ile Leu PheAsp Asp Phe Tyr Ile Leu Glu Ala Ile Leu Asn Pro Lys 305 310 315 320 ArgLeu Asp Val Phe Glu Ala Asp Glu Phe Phe Ala Phe Phe Leu Met 325 330 335Gln Leu Ile Trp Tyr Ile Val Ile Ile Val Leu Ile Val Glu Gly Ser 340 345350 Ser Arg Thr Ile Leu His Ser Ser Tyr Thr Ala Ala Ile Val His Lys 355360 365 Ile Leu Asn Ile Thr Asp Asp Pro Glu Leu Arg Asp Arg Leu Phe Arg370 375 380 Leu Ser Leu Gln Leu Ser His Arg Lys Val Leu Phe Thr Ala AlaGly 385 390 395 400 Leu Phe Arg Leu Asp Arg Thr Leu Ile Phe Thr Val AsnPhe Leu Gln 405 410 415 Ile Thr Gly Ala Ala Thr Cys Tyr Leu Ile Ile LeuIle Gln Phe 420 425 430 6 415 PRT Drosophila melanogaster 6 Met Ile ArgCys Gly Leu Asp Ile Phe Arg Gly Cys Arg Gly Arg Phe 1 5 10 15 Arg TyrTrp Leu Ser Ala Arg Asp Cys Tyr Asp Ser Ile Ser Leu Met 20 25 30 Val AlaIle Ala Phe Ala Leu Gly Ile Thr Pro Phe Leu Val Arg Arg 35 40 45 Asn AlaLeu Gly Glu Asn Ser Leu Glu Gln Ser Trp Tyr Gly Phe Leu 50 55 60 Asn AlaIle Phe Arg Trp Leu Leu Leu Ala Tyr Cys Tyr Ser Tyr Ile 65 70 75 80 AsnLeu Arg Asn Glu Ser Leu Ile Gly Tyr Phe Met Arg Asn His Val 85 90 95 SerGln Ile Ser Thr Arg Val His Asp Val Gly Gly Ile Ile Ala Ala 100 105 110Val Phe Thr Phe Ile Leu Pro Leu Leu Leu Arg Lys Tyr Phe Leu Lys 115 120125 Ser Val Lys Asn Met Val Gln Val Asp Thr Gln Leu Glu Arg Leu Arg 130135 140 Ser Pro Val Asn Phe Asn Thr Val Val Gly Gln Val Val Leu Val Ile145 150 155 160 Leu Ala Val Val Leu Leu Asp Thr Val Leu Leu Thr Thr GlyLeu Val 165 170 175 Cys Leu Ala Lys Met Glu Val Tyr Ala Ser Trp Gln LeuThr Phe Ile 180 185 190 Phe Val Tyr Glu Leu Leu Ala Ile Ser Ile Thr IleCys Met Phe Cys 195 200 205 Leu Met Thr Arg Thr Val Gln Arg Arg Ile ThrCys Leu His Lys Phe 210 215 220 Asp Phe Ala Thr Met Ser Ala Leu Arg ArgVal Arg Lys Tyr Phe Ile 225 230 235 240 Ser Ser Gln Val Tyr Glu Ala LeuArg Pro Leu Phe Phe Leu Thr Phe 245 250 255 Leu Tyr Gly Leu Thr Pro PheHis Val Val Arg Arg Lys Met Gly Glu 260 265 270 Ser Tyr Leu Lys Met SerCys Phe Gly Val Phe Asn Ile Phe Ile Tyr 275 280 285 Ile Cys Leu Cys GlyPhe Cys Tyr Ile Ser Ser Leu Arg Gln Gly Glu 290 295 300 Ser Ile Val GlyTyr Phe Phe Arg Thr Glu Ile Ser Thr Ile Gly Asp 305 310 315 320 Arg LeuGln Ile Phe Asn Gly Leu Ile Ala Gly Ala Val Ile Tyr Thr 325 330 335 SerAla Ile Leu Lys Arg Cys Lys Leu Leu Gly Thr Leu Thr Ile Leu 340 345 350His Ser Leu Asp Thr Asn Phe Ser Asn Ile Gly Val Arg Val Lys Tyr 355 360365 Ser Arg Ile Phe Arg Tyr Ser Leu Leu Val Leu Ile Phe Lys Leu Leu 370375 380 Ile Leu Gly Val Tyr Phe Val Gly Val Phe Arg Leu Leu Val Ser Leu385 390 395 400 Asp Val Thr Pro Ser Phe Cys Val Cys Met Thr Phe Phe LeuGln 405 410 415 7 472 PRT Drosophila melanogaster 7 Met Lys Arg Lys AlaVal Glu Val Ile Gly Leu Ile Pro Leu Asn Arg 1 5 10 15 Gln Gln Ser GluThr Asn Phe Ile Leu Asp Tyr Ala Met Met Cys Ile 20 25 30 Val Pro Ile PheTyr Val Ala Cys Tyr Leu Leu Ile Asn Leu Ser His 35 40 45 Ile Ile Gly LeuCys Leu Leu Asp Ser Cys Asn Ser Val Cys Lys Leu 50 55 60 Ser Ser His LeuPhe Met His Leu Gly Ala Phe Leu Tyr Leu Thr Ile 65 70 75 80 Thr Leu LeuSer Leu Tyr Arg Arg Lys Glu Phe Phe Gln Gln Phe Asp 85 90 95 Ala Arg LeuAsn Asp Ile Asp Ala Val Ile Gln Lys Cys Gln Arg Val 100 105 110 Ala GluMet Asp Lys Val Lys Val Thr Ala Val Lys His Ser Val Ala 115 120 125 TyrHis Phe Thr Trp Leu Phe Leu Phe Cys Val Phe Thr Phe Ala Leu 130 135 140Tyr Tyr Asp Val Arg Ser Leu Tyr Leu Thr Phe Gly Asn Leu Ala Phe 145 150155 160 Ile Pro Phe Met Val Ser Ser Phe Pro Tyr Leu Ala Gly Ser Ile Ile165 170 175 Gln Gly Glu Phe Ile Tyr His Val Ser Val Ile Ser Gln Arg PheGlu 180 185 190 Gln Ile Asn Met Leu Leu Glu Lys Ile Asn Gln Glu Ala ArgHis Arg 195 200 205 His Ala Pro Leu Thr Val Phe Asp Ile Glu Ser Glu GlyLys Lys Glu 210 215 220 Arg Lys Thr Val Thr Pro Ile Thr Val Met Asp GlyArg Thr Thr Thr 225 230 235 240 Gly Phe Gly Asn Glu Asn Lys Phe Ala GlyGlu Met Lys Arg Gln Glu 245 250 255 Gly Gln Gln Lys Asn Asp Asp Asp AspLeu Asp Thr Ser Asn Asp Glu 260 265 270 Asp Glu Asp Asp Phe Asp Tyr AspAsn Ala Thr Ile Ala Glu Asn Thr 275 280 285 Gly Asn Thr Ser Glu Ala AsnLeu Pro Asp Leu Phe Lys Leu His Asp 290 295 300 Lys Ile Leu Ala Leu SerVal Ile Thr Asn Gly Glu Phe Gly Pro Gln 305 310 315 320 Cys Val Pro TyrMet Ala Ala Cys Phe Val Val Ser Ile Phe Gly Ile 325 330 335 Phe Leu GluThr Lys Val Asn Phe Ile Val Gly Gly Lys Ser Arg Leu 340 345 350 Leu AspTyr Met Thr Tyr Leu Tyr Val Ile Trp Ser Phe Thr Thr Met 355 360 365 MetVal Ala Tyr Ile Val Leu Arg Leu Cys Cys Asn Ala Asn Asn His 370 375 380Ser Lys Gln Ser Ala Met Ile Val His Glu Ile Met Gln Lys Lys Pro 385 390395 400 Ala Phe Met Leu Ser Asn Asp Leu Phe Tyr Asn Lys Met Lys Ser Phe405 410 415 Thr Leu Gln Phe Leu His Trp Glu Gly Phe Phe Gln Phe Asn GlyVal 420 425 430 Gly Leu Phe Ala Leu Asp Tyr Thr Phe Ile Phe Ser Thr ValSer Ala 435 440 445 Ala Thr Ser Tyr Leu Ile Val Leu Leu Gln Phe Asp MetThr Ala Ile 450 455 460 Leu Arg Asn Glu Gly Leu Met Ser 465 470 8 390PRT Drosophila melanogaster 8 Met Val Asp Trp Val Val Leu Leu Leu LysAla Val His Ile Tyr Cys 1 5 10 15 Tyr Leu Ile Gly Leu Ser Asn Phe GluPhe Asp Cys Arg Thr Gly Arg 20 25 30 Val Phe Lys Ser Arg Arg Cys Thr IleTyr Ala Phe Met Ala Asn Ile 35 40 45 Phe Ile Leu Ile Thr Ile Ile Tyr AsnPhe Thr Ala His Gly Asp Thr 50 55 60 Asn Leu Leu Phe Gln Ser Ala Asn LysLeu His Glu Tyr Val Ile Ile 65 70 75 80 Ile Met Ser Gly Leu Lys Ile ValAla Leu Ile Thr Val Leu Asn Arg 85 90 95 Trp Leu Gln Arg Gly Gln Met MetGln Leu Val Lys Asp Val Ile Arg 100 105 110 Leu Tyr Met Ile Asn Pro GlnLeu Lys Ser Met Ile Arg Trp Gly Ile 115 120 125 Leu Leu Lys Ala Phe IleSer Phe Ala Ile Glu Leu Leu Gln Val Thr 130 135 140 Leu Ser Val Asp AlaLeu Asp Arg Gln Gly Thr Ala Glu Met Met Gly 145 150 155 160 Leu Leu ValLys Leu Cys Val Ser Phe Ile Met Asn Leu Ala Ile Ser 165 170 175 Gln HisPhe Leu Val Ile Leu Leu Ile Arg Ala Gln Tyr Arg Ile Met 180 185 190 AsnAla Lys Leu Arg Met Val Ile Glu Glu Ser Arg Arg Leu Ser Phe 195 200 205Leu Gln Leu Arg Asn Gly Ala Phe Met Thr Arg Cys Cys Tyr Leu Ser 210 215220 Asp Gln Leu Glu Asp Ile Gly Glu Val Gln Ser Gln Leu Gln Ser Met 225230 235 240 Val Gly Gln Leu Asp Glu Val Phe Gly Met Gln Gly Leu Met AlaTyr 245 250 255 Ser Glu Tyr Tyr Leu Ser Ile Val Gly Thr Ser Tyr Met SerTyr Ser 260 265 270 Ile Tyr Lys Tyr Gly Pro His Asn Leu Lys Leu Ser AlaLys Thr Ser 275 280 285 Ile Ile Val Cys Ile Leu Ile Thr Leu Phe Tyr LeuAsp Ala Leu Val 290 295 300 Asn Cys Asn Asn Met Leu Arg Val Leu Asp HisHis Lys Asp Phe Leu 305 310 315 320 Gly Leu Leu Glu Glu Arg Thr Val PheAla Ser Ser Leu Asp Ile Arg 325 330 335 Leu Glu Glu Ser Val Ser Phe GluSer Leu Gln Leu Gln Leu Ala Arg 340 345 350 Asn Pro Leu Lys Ile Asn ValMet Gly Met Phe Pro Ile Thr Arg Gly 355 360 365 Ser Thr Ala Ala Met CysAla Ser Val Ile Val Asn Ser Ile Phe Leu 370 375 380 Ile Gln Phe Asp MetGlu 385 390 9 344 PRT Drosophila melanogaster 9 Met Asp Leu Glu Ser PheLeu Leu Gly Ala Val Tyr Tyr Tyr Gly Leu 1 5 10 15 Phe Ile Gly Leu SerAsn Phe Glu Phe Asp Trp Asn Thr Gly Arg Val 20 25 30 Phe Thr Lys Lys TrpSer Thr Leu Tyr Ala Ile Ala Leu Asp Ser Cys 35 40 45 Ile Phe Ala Leu TyrIle Tyr His Trp Thr Gly Asn Thr Asn Ile Val 50 55 60 Asn Ala Ile Phe GlyArg Ala Asn Met Leu His Glu Tyr Val Val Ala 65 70 75 80 Ile Leu Thr GlyLeu Arg Ile Val Thr Gly Leu Phe Thr Leu Ile Leu 85 90 95 Arg Trp Tyr GlnArg Cys Lys Met Met Asp Leu Ala Ser Lys Val Val 100 105 110 Arg Met TyrVal Ala Arg Pro Gln Val Arg Arg Met Ser Arg Trp Gly 115 120 125 Ile LeuThr Lys Phe Ile Phe Gly Ser Ile Thr Asp Gly Leu Gln Met 130 135 140 AlaMet Val Leu Ser Ala Met Gly Ser Arg Val Asp Ser Gln Phe Tyr 145 150 155160 Leu Gly Leu Gly Leu Gln Tyr Trp Met Phe Val Ile Leu Asn Met Ala 165170 175 Met Met Gln Gln His Met Ile Met Leu Phe Val Arg Thr Gln Phe Gln180 185 190 Leu Ile Asn Thr Glu Leu Arg Gln Val Ile Asp Glu Ala Lys AspLeu 195 200 205 Leu Leu Ser Pro Arg His Gln Gly Val Phe Met Thr Lys CysCys Ser 210 215 220 Leu Ala Asp Gln Ile Glu Asn Ile Ala Arg Ile Gln SerGln Leu Gln 225 230 235 240 Thr Ile Met Asn Gln Met Glu Glu Val Phe GlyIle Gln Gly Ala Met 245 250 255 Thr Tyr Gly Gly Tyr Tyr Leu Ser Ser ValGly Thr Cys Tyr Leu Ala 260 265 270 Tyr Ser Ile Leu Lys His Gly Tyr GluAsn Leu Ser Met Thr Leu Ser 275 280 285 Thr Val Ile Leu Ala Tyr Ser TrpCys Phe Phe Tyr Tyr Leu Asp Gly 290 295 300 Met Leu Asn Leu Ser Val MetLeu His Val Gln Asp Asp Tyr Trp Glu 305 310 315 320 Met Leu Gln Ile LeuGly Lys Arg Thr Ile Phe Val Gly Leu Asp Val 325 330 335 Arg Leu Glu GluAla Val Ser Thr 340 10 383 PRT Drosophila melanogaster 10 Met Ile LysLeu Tyr Phe Arg Tyr Ser Leu Ala Ile Gly Ile Thr Ser 1 5 10 15 Gln GlnPhe Ser Asn Arg Lys Phe Phe Ser Thr Leu Phe Ser Arg Thr 20 25 30 Tyr AlaLeu Ile Ala Asn Ile Val Thr Leu Ile Met Leu Pro Ile Val 35 40 45 Met TrpGln Val Gln Leu Val Phe Gln Gln Lys Lys Thr Phe Pro Lys 50 55 60 Leu IleLeu Ile Thr Asn Asn Val Arg Glu Ala Val Ser Phe Leu Val 65 70 75 80 IleLeu Tyr Thr Val Leu Ser Arg Gly Phe Arg Asp Thr Ala Phe Lys 85 90 95 GluMet Gln Pro Leu Leu Leu Thr Leu Phe Arg Glu Glu Lys Arg Cys 100 105 110Gly Phe Lys Gly Ile Gly Gly Val Arg Arg Ser Leu Arg Ile Leu Leu 115 120125 Phe Val Lys Phe Phe Thr Leu Ser Trp Leu Cys Val Thr Asp Val Leu 130135 140 Phe Leu Leu Tyr Ser Thr Asp Ala Leu Ile Trp Val Asn Val Leu Arg145 150 155 160 Phe Phe Phe Lys Cys Asn Thr Asn Asn Ile Leu Glu Met ValPro Met 165 170 175 Gly Tyr Phe Leu Ala Leu Trp His Ile Ala Arg Gly PheAsp Cys Val 180 185 190 Asn Arg Arg Leu Asp Gln Ile Val Lys Ser Lys SerThr Arg Lys His 195 200 205 Arg Glu Leu Gln His Leu Trp Leu Leu His AlaCys Leu Thr Lys Thr 210 215 220 Ala Leu Asn Ile Asn Lys Ile Tyr Ala ProGln Met Leu Ala Ser Arg 225 230 235 240 Phe Asp Asn Phe Val Asn Gly ValIle Gln Ala Tyr Trp Gly Ala Val 245 250 255 Phe Thr Phe Asp Leu Ser ThrPro Phe Phe Trp Val Val Tyr Gly Ser 260 265 270 Val Gln Tyr His Val ArgCys Leu Asp Tyr Tyr Leu Ile Asp Asn Met 275 280 285 Cys Asp Val Ala ValGlu Tyr His Asp Ser Ala Lys His Ser Trp Ser 290 295 300 Glu Val Arg TrpThr Lys Glu Val Ser Ala Phe Gly Ser Ile Leu Leu 305 310 315 320 Tyr IleCys Met Leu Met Gln Leu Leu Ser Phe Gln Ile Ser Ser Tyr 325 330 335 ValIle Tyr Ala Asn Ser Thr Lys Leu Gln Leu Trp Ser Cys Gly Leu 340 345 350Phe Gln Ala Asn Arg Ser Met Trp Phe Ala Met Ile Ser Ser Val Leu 355 360365 Tyr Tyr Ile Leu Val Leu Leu Gln Phe His Leu Val Met Arg Lys 370 375380 11 436 PRT Drosophila melanogaster 11 Met Ser Arg Thr Ser Asp AspIle Arg Lys His Leu Lys Val Arg Arg 1 5 10 15 Gln Lys Gln Arg Ala IleLeu Ala Met Arg Trp Arg Cys Ala Gln Gly 20 25 30 Gly Leu Glu Phe Glu GlnLeu Asp Thr Phe Tyr Gly Ala Ile Arg Pro 35 40 45 Tyr Leu Cys Val Ala GlnPhe Phe Gly Ile Met Pro Leu Ser Asn Ile 50 55 60 Arg Ser Arg Asp Pro GlnAsp Val Lys Phe Lys Val Arg Ser Ile Gly 65 70 75 80 Leu Ala Val Thr GlyLeu Phe Leu Leu Leu Gly Gly Met Lys Thr Leu 85 90 95 Val Gly Ala Asn IleLeu Phe Thr Glu Gly Leu Asn Ala Lys Asn Ile 100 105 110 Val Gly Leu ValPhe Leu Ile Val Gly Met Val Asn Trp Leu Asn Phe 115 120 125 Val Gly PheAla Arg Ser Trp Ser His Ile Met Leu Pro Trp Ser Ser 130 135 140 Val AspIle Leu Met Leu Phe Pro Pro Tyr Lys Arg Gly Lys Arg Ser 145 150 155 160Leu Arg Ser Lys Val Asn Val Leu Ala Leu Ser Val Val Val Leu Ala 165 170175 Val Gly Asp His Met Leu Tyr Tyr Ala Ser Gly Tyr Cys Ser Tyr Ser 180185 190 Met His Ile Leu Gln Cys His Thr Asn His Ser Arg Ile Thr Phe Gly195 200 205 Leu Tyr Leu Glu Lys Glu Phe Ser Asp Ile Met Phe Ile Met ProPhe 210 215 220 Asn Ile Phe Ser Met Cys Tyr Gly Phe Trp Leu Asn Gly AlaPhe Thr 225 230 235 240 Phe Leu Trp Asn Phe Met Asp Ile Phe Ile Val MetThr Ser Ile Gly 245 250 255 Leu Ala Gln Arg Phe Gln Gln Phe Ala Ala ArgVal Gly Ala Leu Glu 260 265 270 Gly Arg His Val Pro Glu Ala Leu Trp TyrAsp Ile Arg Arg Asp His 275 280 285 Ile Arg Leu Cys Glu Leu Ala Ser LeuVal Glu Ala Ser Met Ser Asn 290 295 300 Ile Val Phe Val Ser Cys Ala AsnAsn Val Tyr Val Ile Cys Asn Gln 305 310 315 320 Ala Leu Ala Ile Phe ThrLys Leu Arg His Pro Ile Asn Tyr Val Tyr 325 330 335 Phe Trp Tyr Ser LeuIle Phe Leu Leu Ala Arg Thr Ser Leu Val Phe 340 345 350 Met Thr Ala SerLys Ile His Asp Ala Ser Leu Leu Pro Leu Arg Ser 355 360 365 Leu Tyr LeuVal Pro Ser Asp Gly Trp Thr Gln Glu Val Gln Arg Phe 370 375 380 Ala AspGln Leu Thr Ser Glu Phe Val Gly Leu Ser Gly Tyr Arg Leu 385 390 395 400Phe Cys Leu Thr Arg Lys Ser Leu Phe Gly Met Leu Ala Thr Leu Val 405 410415 Thr Tyr Glu Leu Met Leu Leu Gln Ile Asp Ala Lys Ser His Lys Gly 420425 430 Leu Arg Cys Ala 435 12 512 PRT Drosophila melanogaster 12 MetArg Pro Ser Gly Glu Lys Val Val Lys Gly His Gly Gln Gly Asn 1 5 10 15Ser Gly His Ser Leu Ser Gly Met Ala Asn Tyr Tyr Arg Arg Lys Lys 20 25 30Gly Asp Ala Val Phe Leu Asn Ala Lys Pro Leu Asn Ser Ala Asn Ala 35 40 45Gln Ala Tyr Leu Tyr Gly Val Arg Lys Tyr Ser Ile Gly Leu Ala Glu 50 55 60Arg Leu Asp Ala Asp Tyr Glu Ala Pro Pro Leu Asp Arg Lys Lys Ser 65 70 7580 Ser Asp Ser Thr Ala Ser Asn Asn Pro Glu Phe Lys Pro Ser Val Phe 85 9095 Tyr Arg Asn Ile Asp Pro Ile Asn Trp Phe Leu Arg Ile Ile Gly Val 100105 110 Leu Pro Ile Val Arg His Gly Pro Ala Arg Ala Lys Phe Glu Met Asn115 120 125 Ser Ala Ser Phe Ile Tyr Ser Val Val Phe Phe Val Leu Leu AlaCys 130 135 140 Tyr Val Gly Tyr Val Ala Asn Asn Arg Ile His Ile Val ArgSer Leu 145 150 155 160 Ser Gly Pro Phe Glu Glu Ala Val Ile Ala Tyr LeuPhe Leu Val Asn 165 170 175 Ile Leu Pro Ile Met Ile Ile Pro Ile Leu TrpTyr Glu Ala Arg Lys 180 185 190 Ile Ala Lys Leu Phe Asn Asp Trp Asp AspPhe Glu Val Leu Tyr Tyr 195 200 205 Gln Ile Ser Gly His Ser Leu Pro LeuLys Leu Arg Gln Lys Ala Val 210 215 220 Tyr Ile Ala Ile Val Leu Pro IleLeu Ser Val Leu Ser Val Val Ile 225 230 235 240 Thr His Val Thr Met SerAsp Leu Asn Ile Asn Gln Val Val Pro Tyr 245 250 255 Cys Ile Leu Asp AsnLeu Thr Ala Met Leu Gly Ala Trp Trp Phe Leu 260 265 270 Ile Cys Glu AlaMet Ser Ile Thr Ala His Leu Leu Ala Glu Arg Phe 275 280 285 Gln Lys AlaLeu Lys His Ile Gly Pro Ala Ala Met Val Ala Asp Tyr 290 295 300 Arg ValLeu Trp Leu Arg Leu Ser Lys Leu Thr Arg Asp Thr Gly Asn 305 310 315 320Ala Leu Cys Tyr Thr Phe Val Phe Met Ser Leu Tyr Leu Phe Phe Ile 325 330335 Ile Thr Leu Ser Ile Tyr Gly Leu Met Ser Gln Leu Ser Glu Gly Phe 340345 350 Gly Ile Lys Asp Ile Gly Leu Thr Ile Thr Ala Leu Trp Asn Ile Gly355 360 365 Leu Leu Phe Tyr Ile Cys Asp Glu Ala His Tyr Ala Ser Val AsnVal 370 375 380 Arg Thr Asn Phe Gln Lys Lys Leu Leu Met Val Glu Leu AsnTrp Met 385 390 395 400 Asn Ser Asp Ala Gln Thr Glu Ile Asn Met Phe LeuArg Ala Thr Glu 405 410 415 Met Asn Pro Ser Thr Ile Asn Cys Gly Gly PhePhe Asp Val Asn Arg 420 425 430 Thr Leu Phe Lys Gly Leu Leu Thr Thr MetVal Thr Tyr Leu Val Val 435 440 445 Leu Leu Gln Phe Gln Ile Ser Ile ProThr Asp Lys Gly Asp Ser Glu 450 455 460 Gly Ala Asn Asn Ile Thr Val ValAsp Phe Val Met Asp Ser Leu Asp 465 470 475 480 Asn Asp Met Ser Leu MetGly Ala Ser Thr Leu Ser Thr Thr Thr Val 485 490 495 Gly Thr Thr Leu ProPro Pro Ile Met Lys Leu Lys Gly Arg Lys Gly 500 505 510 13 367 PRTDrosophila melanogaster 13 Met Pro Val Arg Lys Val Ser Ser Lys Phe AlaGlu Asp Leu Thr Phe 1 5 10 15 Thr Trp Phe Ser Val Arg Ser Tyr Tyr AlaLeu Val Thr Ile Leu Phe 20 25 30 Phe Gly Val Ser Ser Gly Tyr Met Val AlaPhe Val Thr Ser Val Ser 35 40 45 Phe Asn Phe Asp Ser Val Glu Thr Leu ValPhe Tyr Leu Ser Ile Phe 50 55 60 Leu Ile Ser Leu Ser Phe Phe Gln Leu AlaArg Lys Trp Pro Glu Ile 65 70 75 80 Ala Gln Ser Trp Gln Leu Val Glu AlaLys Leu Pro Pro Leu Lys Leu 85 90 95 Pro Lys Glu Arg Arg Ser Leu Ala GlnHis Ile Asn Met Ile Thr Ile 100 105 110 Val Ala Thr Thr Cys Ser Leu ValGlu His Ile Met Ser Met Leu Ser 115 120 125 Met Gly Tyr Tyr Val Asn SerCys Pro Arg Trp Pro Asp Arg Pro Ile 130 135 140 Asp Ser Phe Leu Tyr LeuSer Phe Ser Ser Val Phe Tyr Phe Val Asp 145 150 155 160 Tyr Thr Arg PheLeu Gly Ile Val Gly Lys Val Val Asn Val Leu Ser 165 170 175 Thr Phe AlaTrp Asn Phe Asn Asp Ile Phe Val Met Ala Val Ser Val 180 185 190 Ala LeuAla Ala Arg Phe Arg Gln Leu Asn Asp Tyr Met Met Arg Glu 195 200 205 AlaArg Leu Pro Thr Thr Val Asp Tyr Trp Met Gln Cys Arg Ile Asn 210 215 220Phe Arg Asn Leu Cys Lys Leu Cys Glu Glu Val Asp Asp Ala Ile Ser 225 230235 240 Thr Ile Thr Leu Leu Cys Phe Ser Asn Asn Leu Tyr Phe Ile Cys Gly245 250 255 Lys Ile Leu Lys Ser Met Gln Ala Lys Pro Ser Ile Trp His AlaLeu 260 265 270 Tyr Phe Trp Phe Ser Leu Val Tyr Leu Leu Gly Arg Thr LeuIle Leu 275 280 285 Ser Leu Tyr Ser Ser Ser Ile Asn Asp Glu Ser Lys ArgPro Leu Val 290 295 300 Ile Phe Arg Leu Val Pro Arg Glu Tyr Trp Cys AspGlu Leu Lys Arg 305 310 315 320 Phe Ser Glu Glu Val Gln Met Asp Asn ValAla Leu Thr Gly Met Lys 325 330 335 Phe Phe Arg Leu Thr Arg Gly Val ValIle Ser Val Ala Gly Thr Ile 340 345 350 Val Thr Tyr Glu Leu Ile Leu LeuGln Phe Asn Gly Glu Glu Lys 355 360 365 14 409 PRT Drosophilamelanogaster 14 Met Glu Leu Ser Arg Ser Asp Lys Glu Ala Phe Leu Ser AspGly Ser 1 5 10 15 Phe His Gln Ala Val Gly Arg Val Leu Leu Val Ala GluPhe Phe Ala 20 25 30 Met Met Pro Val Lys Gly Val Thr Gly Lys His Pro SerAsp Leu Ser 35 40 45 Phe Ser Trp Arg Asn Ile Arg Thr Cys Phe Ser Leu LeuPhe Ile Ala 50 55 60 Ser Ser Leu Ala Asn Phe Gly Leu Ser Leu Phe Lys ValLeu Asn Asn 65 70 75 80 Pro Ile Ser Phe Asn Ser Ile Lys Pro Ile Ile PheArg Gly Ser Val 85 90 95 Leu Leu Val Leu Ile Val Ala Leu Asn Leu Ala ArgGln Trp Pro Gln 100 105 110 Leu Met Met Tyr Trp His Thr Val Glu Lys AspLeu Pro Gln Tyr Lys 115 120 125 Thr Gln Leu Thr Lys Trp Lys Met Gly HisThr Ile Ser Met Val Met 130 135 140 Leu Leu Gly Met Met Leu Ser Phe AlaGlu His Ile Leu Ser Met Val 145 150 155 160 Ser Ala Ile Asn Tyr Ala SerPhe Cys Asn Arg Thr Ala Asp Pro Ile 165 170 175 Gln Asn Tyr Phe Leu ArgThr Asn Asp Glu Ile Phe Phe Val Thr Ser 180 185 190 Tyr Ser Thr Thr LeuAla Leu Trp Gly Lys Phe Gln Asn Val Phe Ser 195 200 205 Thr Phe Ile TrpAsn Tyr Met Asp Leu Phe Val Met Ile Val Ser Ile 210 215 220 Gly Leu AlaSer Lys Phe Arg Gln Leu Asn Asp Asp Leu Arg Asn Phe 225 230 235 240 LysGly Met Asn Met Ala Pro Ser Tyr Trp Ser Glu Arg Arg Ile Gln 245 250 255Tyr Arg Asn Ile Cys Ile Leu Cys Asp Lys Met Asp Asp Ala Ile Ser 260 265270 Leu Ile Thr Met Val Ser Phe Ser Asn Asn Leu Tyr Phe Ile Cys Val 275280 285 Gln Leu Leu Arg Ser Leu Asn Thr Met Pro Ser Val Ala His Ala Val290 295 300 Tyr Phe Tyr Phe Ser Leu Ile Phe Leu Ile Gly Arg Thr Leu AlaVal 305 310 315 320 Ser Leu Tyr Ser Ser Ser Val His Asp Glu Ser Arg LeuThr Leu Arg 325 330 335 Tyr Leu Arg Cys Val Pro Lys Glu Ser Trp Cys ProGlu Val Lys Arg 340 345 350 Phe Thr Glu Glu Val Ile Ser Asp Glu Val AlaLeu Thr Gly Met Lys 355 360 365 Phe Phe His Leu Thr Arg Lys Leu Val LeuSer Val Ala Gly Thr Ile 370 375 380 Val Thr Tyr Glu Leu Val Leu Ile GlnPhe His Glu Asp Asn Asp Leu 385 390 395 400 Trp Asp Cys Asp Gln Ser TyrTyr Ser 405 15 498 PRT Drosophila melanogaster 15 Met Asp Asn Met AlaGln Ala Glu Asp Ala Val Gln Pro Leu Leu Gln 1 5 10 15 Gln Phe Gln GlnLeu Phe Phe Ile Ser Lys Ile Ala Gly Ile Leu Pro 20 25 30 Gln Asp Leu GluLys Phe Arg Ser Arg Asn Leu Leu Glu Lys Ser Arg 35 40 45 Asn Gly Met IleTyr Met Leu Ser Thr Leu Ile Leu Tyr Val Val Leu 50 55 60 Tyr Asn Ile LeuIle Tyr Ser Phe Gly Glu Glu Asp Arg Ser Leu Lys 65 70 75 80 Ala Ser GlnSer Thr Leu Thr Phe Val Ile Gly Leu Phe Leu Thr Tyr 85 90 95 Ile Gly LeuIle Met Met Val Ser Asp Gln Leu Thr Ala Leu Arg Asn 100 105 110 Gln GlyArg Ile Gly Glu Leu Tyr Glu Arg Ile Arg Leu Val Asp Glu 115 120 125 ArgLeu Tyr Lys Glu Gly Cys Val Met Asp Asn Ser Thr Ile Gly Arg 130 135 140Arg Ile Arg Ile Met Leu Ile Met Thr Val Ile Phe Glu Leu Ser Ile 145 150155 160 Leu Val Ser Thr Tyr Val Lys Leu Val Asp Tyr Ser Gln Trp Met Ser165 170 175 Leu Leu Trp Ile Val Ser Ala Ile Pro Thr Phe Ile Asn Thr LeuAsp 180 185 190 Lys Ile Trp Phe Ala Val Ser Leu Tyr Ala Leu Lys Glu ArgPhe Glu 195 200 205 Ala Ile Asn Ala Thr Leu Glu Glu Leu Val Asp Thr HisGlu Lys His 210 215 220 Lys Leu Trp Leu Arg Gly Asn Gln Glu Val Pro ProPro Leu Asp Ser 225 230 235 240 Ser Gln Pro Pro Gln Tyr Asp Ser Asn LeuGlu Tyr Leu Tyr Lys Glu 245 250 255 Leu Gly Ala Ile Asp Ala Ala Ser ArgLys Pro Pro Pro Pro Pro Leu 260 265 270 Ala Thr Asn Met Val His Glu SerGlu Leu Gly Asn Ala Ala Lys Val 275 280 285 Glu Glu Lys Leu Asn Asn LeuCys Gln Val His Asp Glu Ile Cys Glu 290 295 300 Ile Gly Lys Ala Leu AsnGlu Leu Trp Ser Tyr Pro Ile Leu Ser Leu 305 310 315 320 Met Ala Tyr GlyPhe Leu Ile Phe Thr Ala Gln Leu Tyr Phe Leu Tyr 325 330 335 Cys Ala ThrGln Tyr Gln Ser Ile Pro Ser Leu Phe Arg Ser Ala Lys 340 345 350 Asn ProPhe Ile Thr Val Ile Val Leu Ser Tyr Thr Ser Gly Lys Cys 355 360 365 ValTyr Leu Ile Tyr Leu Ser Trp Lys Thr Ser Gln Ala Ser Lys Arg 370 375 380Thr Gly Ile Ser Leu His Lys Cys Gly Val Val Ala Asp Asp Asn Leu 385 390395 400 Leu Tyr Glu Ile Val Asn His Leu Ser Leu Lys Leu Leu Asn His Ser405 410 415 Val Asp Phe Ser Ala Cys Gly Phe Phe Thr Leu Asp Met Glu ThrLeu 420 425 430 Tyr Gly Val Ser Gly Gly Ile Thr Ser Tyr Leu Ile Ile LeuIle Gln 435 440 445 Phe Asn Leu Ala Ala Gln Gln Ala Lys Glu Ala Ile GlnThr Phe Asn 450 455 460 Ser Leu Asn Asp Thr Ala Gly Leu Val Gly Ala AlaThr Asp Met Asp 465 470 475 480 Asn Ile Ser Ser Thr Leu Arg Asp Phe ValThr Thr Thr Met Thr Pro 485 490 495 Ala Val 16 346 PRT Drosophilamelanogaster 16 Met Phe Glu Phe Leu His Gln Met Ser Ala Pro Lys Leu SerThr Ser 1 5 10 15 Ile Leu Arg Tyr Ile Phe Arg Tyr Ala Gln Phe Ile GlyVal Ile Phe 20 25 30 Phe Cys Leu His Thr Arg Lys Asp Asp Lys Thr Val PheIle Arg Asn 35 40 45 Trp Leu Lys Trp Leu Asn Val Thr His Arg Ile Ile ThrPhe Thr Arg 50 55 60 Phe Phe Trp Val Tyr Ile Ala Ser Ile Ser Ile Lys ThrAsn Arg Val 65 70 75 80 Leu Gln Val Leu His Gly Met Arg Leu Val Leu SerIle Pro Asn Val 85 90 95 Ala Val Ile Leu Cys Tyr His Ile Phe Arg Gly ProGlu Ile Ile Asp 100 105 110 Leu Ile Asn Gln Phe Leu Arg Leu Phe Arg GlnVal Ser Asp Leu Phe 115 120 125 Lys Thr Lys Thr Pro Gly Phe Gly Gly ArgArg Glu Leu Ile Leu Ile 130 135 140 Leu Leu Asn Leu Ile Ser Phe Ala HisGlu Gln Thr Tyr Leu Trp Phe 145 150 155 160 Thr Ile Arg Lys Gly Phe SerTrp Arg Phe Leu Ile Asp Trp Trp Cys 165 170 175 Asp Phe Tyr Leu Val SerAla Thr Asn Ile Phe Ile His Ile Asn Ser 180 185 190 Ile Gly Tyr Leu SerLeu Gly Val Leu Tyr Ser Glu Leu Asn Lys Tyr 195 200 205 Val Tyr Thr AsnLeu Arg Ile Gln Leu Gln Lys Leu Asn Thr Ser Gly 210 215 220 Ser Lys GlnLys Ile Arg Arg Val Gln Asn Arg Leu Glu Lys Cys Ile 225 230 235 240 SerLeu Tyr Arg Glu Ile Tyr His Thr Ser Ile Met Phe His Lys Leu 245 250 255Phe Val Pro Leu Leu Phe Leu Ala Leu Ile Tyr Lys Val Leu Leu Ile 260 265270 Ala Leu Ile Gly Phe Asn Val Ala Val Glu Phe Tyr Leu Asn Ser Phe 275280 285 Ile Phe Trp Ile Leu Leu Gly Lys His Val Leu Asp Leu Phe Leu Val290 295 300 Thr Val Ser Val Glu Gly Ala Val Asn Gln Phe Leu Asn Ile GlyMet 305 310 315 320 Gln Phe Gly Asn Val Gly Asp Leu Ser Lys Phe Gln ThrThr Val Ser 325 330 335 Gln Phe Ile Phe Ile Asp Phe Ile Pro Ile 340 34517 736 PRT Drosophila melanogaster 17 Met Val Ala Gln Lys Ser Arg LeuLeu Ala Arg Ala Phe Pro Tyr Leu 1 5 10 15 Asp Ile Phe Ser Val Phe AlaLeu Thr Pro Pro Pro Gln Ser Phe Gly 20 25 30 His Thr Pro His Arg Arg LeuArg Trp Tyr Leu Met Thr Gly Tyr Val 35 40 45 Phe Tyr Ala Thr Ala Ile LeuAla Thr Val Phe Ile Val Ser Tyr Phe 50 55 60 Asn Ile Ile Ala Ile Asp GluGlu Val Leu Glu Tyr Asn Val Ser Asp 65 70 75 80 Phe Thr Arg Val Met GlyAsn Ile Gln Lys Ser Leu Tyr Ser Ile Met 85 90 95 Ala Ile Ala Asn His LeuAsn Met Leu Ile Asn Tyr Arg Arg Leu Gly 100 105 110 Gly Ile Tyr Lys AspIle Ala Asp Leu Glu Met Asp Met Asp Glu Ala 115 120 125 Ser Gln Cys PheGly Gly Gln Arg Gln Arg Phe Ser Phe Arg Phe Arg 130 135 140 Met Ala LeuCys Val Gly Val Trp Met Ile Leu Met Val Gly Ser Met 145 150 155 160 ProArg Leu Thr Met Thr Ala Met Gly Pro Phe Val Ser Thr Leu Leu 165 170 175Lys Ile Leu Thr Glu Phe Val Met Ile Met Gln Gln Leu Lys Ser Leu 180 185190 Glu Tyr Cys Val Phe Val Leu Ile Ile Tyr Glu Leu Val Leu Arg Leu 195200 205 Arg Arg Thr Leu Ser Gln Leu Gln Glu Glu Phe Gln Asp Cys Glu Gln210 215 220 Gln Asp Met Leu Gln Ala Leu Cys Val Ala Leu Lys Arg Asn GlnLeu 225 230 235 240 Leu Leu Gly Arg Ile Trp Arg Leu Glu Gly Asp Val GlySer Tyr Phe 245 250 255 Thr Pro Thr Met Leu Leu Leu Phe Leu Tyr Asn GlyLeu Thr Ile Leu 260 265 270 His Met Val Asn Trp Ala Tyr Ile Asn Lys PheLeu Tyr Asp Ser Cys 275 280 285 Cys Gln Tyr Gly Pro Glu Tyr Cys Leu PheVal Leu Leu Val Tyr Glu 290 295 300 Leu Ile Leu Arg Thr Arg His Val LeuGlu Gln Leu Lys Asp Asp Leu 305 310 315 320 Glu Asp Phe Asp Cys Gly AlaArg Ile Gln Glu Leu Cys Val Thr Leu 325 330 335 Lys Gln Asn Gln Leu LeuIle Gly Arg Ile Trp Arg Leu Val Asp Glu 340 345 350 Ile Gly Ala Tyr PheArg Trp Ser Met Thr Leu Leu Phe Leu Tyr Asn 355 360 365 Gly Leu Thr IleLeu His Val Val Asn Trp Ala Ile Ile Arg Ser Ile 370 375 380 Asp Pro AsnAsp Cys Cys Gln Leu Met Ser Phe His Phe Ser Leu Asn 385 390 395 400 MetGlu Ala Asn Arg Ser Arg Leu Leu Ala Ala Ala Arg Pro Tyr Ile 405 410 415Gln Ile Tyr Ser Ile Phe Gly Leu Thr Pro Pro Ile Gln Phe Phe Thr 420 425430 Arg Thr Leu His Lys Arg Arg Arg Gly Ile Val Ile Leu Gly Tyr Ala 435440 445 Cys Tyr Leu Ile Ser Ile Ser Leu Met Val Ile Tyr Glu Cys Tyr Ala450 455 460 Asn Ile Val Ala Leu Gln Lys Asp Ile His Lys Phe His Ala GluAsp 465 470 475 480 Ser Ser Lys Val Met Gly Asn Thr Gln Lys Val Leu ValVal Ala Met 485 490 495 Phe Val Trp Asn Gln Leu Asn Ile Leu Leu Asn PheArg Arg Leu Ala 500 505 510 Arg Ile Tyr Asp Asp Ile Ala Asp Leu Glu IleAsp Leu Asn Asn Ala 515 520 525 Ser Ser Gly Phe Val Gly Gln Arg His TrpTrp Arg Phe Arg Phe Arg 530 535 540 Leu Ala Leu Ser Val Gly Leu Trp IleVal Leu Leu Val Gly Leu Thr 545 550 555 560 Pro Arg Phe Thr Leu Val AlaLeu Gly Pro Tyr Leu His Trp Thr Asn 565 570 575 Lys Val Leu Thr Glu IleIle Leu Ile Met Leu Gln Leu Lys Cys Thr 580 585 590 Glu Tyr Cys Val PheVal Leu Leu Ile Tyr Glu Leu Ile Leu Arg Gly 595 600 605 Arg His Ile LeuGln Gln Ile Ser Val Glu Leu Glu Gly Asn Gln Ser 610 615 620 Arg Asp SerVal Gln Glu Leu Cys Val Ala Leu Lys Arg Asn Gln Leu 625 630 635 640 LeuAla Gly Arg Ile Trp Gly Leu Val Asn Glu Val Ser Leu Tyr Phe 645 650 655Thr Leu Ser Leu Thr Leu Leu Phe Leu Tyr Asn Glu Leu Thr Ile Leu 660 665670 Gln Ile Val Asn Trp Ala Leu Ile Lys Ser Val Asn Pro Asn Glu Cys 675680 685 Cys Gln Tyr Thr Glu Asp Tyr Leu Ile Leu Lys Met Gly Leu Arg Glu690 695 700 Tyr Ser Leu Gln Met Glu His Leu Lys Leu Ile Phe Thr Cys GlyGly 705 710 715 720 Leu Phe Asp Ile Asn Leu Lys Phe Phe Gly Gly Val LysLeu Lys Leu 725 730 735 18 294 PRT Drosophila melanogaster 18 Met GluAla Lys Arg Ser Arg Leu Leu Thr Thr Ala Arg Pro Tyr Leu 1 5 10 15 GlnVal Leu Ser Leu Phe Gly Leu Thr Pro Pro Ala Glu Phe Phe Thr 20 25 30 ArgThr Leu Arg Lys Arg Arg Arg Phe Cys Trp Met Ala Gly Tyr Ser 35 40 45 LeuTyr Leu Ile Ala Ile Leu Leu Met Val Phe Tyr Glu Phe His Ala 50 55 60 AsnIle Val Ser Leu His Leu Glu Ile Tyr Lys Phe His Val Glu Asp 65 70 75 80Phe Ser Lys Val Met Gly Arg Thr Gln Lys Phe Leu Ile Val Ala Ile 85 90 95Ala Thr Cys Asn Gln Leu Asn Ile Leu Leu Asn Tyr Gly Arg Leu Gly 100 105110 Leu Ile Tyr Asp Glu Ile Ala Asn Leu Asp Leu Gly Ile Asp Lys Ser 115120 125 Ser Lys Asn Phe Cys Gly Lys Ser His Trp Trp Ser Phe Arg Leu Arg130 135 140 Leu Thr Leu Ser Ile Gly Leu Trp Met Val Ile Ile Ile Gly ValIle 145 150 155 160 Pro Arg Leu Thr Leu Gly Arg Ala Gly Pro Phe Phe HisTrp Val Asn 165 170 175 Gln Val Leu Thr Gln Ile Ile Leu Ile Met Leu GlnLeu Lys Gly Pro 180 185 190 Glu Tyr Cys Leu Phe Val Leu Leu Val Tyr GluLeu Ile Leu Arg Thr 195 200 205 Arg His Val Leu Glu Gln Leu Lys Asp AspLeu Glu Asp Phe Asp Cys 210 215 220 Gly Ala Arg Ile Gln Glu Leu Cys ValThr Leu Lys Gln Asn Gln Leu 225 230 235 240 Leu Ile Gly Arg Ile Trp ArgLeu Val Asp Glu Ile Gly Ala Tyr Phe 245 250 255 Arg Trp Ser Met Thr LeuLeu Phe Leu Tyr Asn Gly Leu Thr Ile Leu 260 265 270 His Val Val Asn TrpAla Ile Ile Arg Ser Ile Asp Pro Asn Asp Cys 275 280 285 Cys Gln Leu SerGlu Glu 290 19 398 PRT Drosophila melanogaster 19 Met Phe Arg Pro SerGly Ser Gly Tyr Arg Gln Lys Trp Thr Gly Leu 1 5 10 15 Thr Leu Lys GlyAla Leu Tyr Gly Ser Trp Ile Leu Gly Val Phe Pro 20 25 30 Phe Ala Tyr AspSer Trp Thr Arg Thr Leu Arg Arg Ser Lys Trp Leu 35 40 45 Ile Ala Tyr GlyPhe Val Leu Asn Ala Ala Phe Ile Leu Leu Val Val 50 55 60 Thr Asn Asp ThrGlu Ser Glu Thr Pro Leu Arg Met Glu Val Phe His 65 70 75 80 Arg Asn AlaLeu Ala Glu Gln Ile Asn Gly Ile His Asp Ile Gln Ser 85 90 95 Leu Ser MetVal Ser Ile Met Leu Leu Arg Ser Phe Trp Lys Ser Gly 100 105 110 Asp IleGlu Arg Thr Leu Asn Glu Leu Glu Asp Leu Gln His Arg Tyr 115 120 125 PheArg Asn Tyr Ser Leu Glu Glu Cys Ile Ser Phe Asp Arg Phe Val 130 135 140Leu Tyr Lys Gly Phe Ser Val Val Leu Glu Leu Val Ser Met Leu Val 145 150155 160 Leu Glu Leu Gly Met Ser Pro Asn Tyr Ser Ala Gln Phe Phe Ile Gly165 170 175 Leu Gly Ser Leu Cys Leu Met Leu Leu Ala Val Leu Leu Gly AlaSer 180 185 190 His Phe His Leu Ala Val Val Phe Val Tyr Arg Tyr Val TrpIle Val 195 200 205 Asn Arg Glu Leu Leu Lys Leu Val Asn Lys Met Ala IleGly Glu Thr 210 215 220 Val Glu Ser Glu Arg Met Asp Leu Leu Leu Tyr LeuTyr His Arg Leu 225 230 235 240 Leu Asp Leu Gly Gln Arg Leu Ala Ser IleTyr Asp Tyr Gln Met Val 245 250 255 Met Val Met Val Ser Phe Leu Ile AlaAsn Val Leu Gly Ile Tyr Phe 260 265 270 Phe Ile Ile Tyr Ser Ile Ser LeuAsn Lys Ser Leu Asp Phe Lys Ile 275 280 285 Leu Val Phe Val Gln Ala LeuVal Ile Asn Met Leu Asp Phe Trp Leu 290 295 300 Asn Val Glu Ile Cys GluLeu Ala Glu Arg Thr Gly Arg Gln Thr Ser 305 310 315 320 Thr Ile Leu LysLeu Phe Asn Asp Ile Glu Asn Ile Asp Glu Lys Leu 325 330 335 Glu Arg SerVal Ser Phe Thr Ser Gln His Tyr Cys Glu Thr Asp Phe 340 345 350 Ala LeuPhe Cys Ser His Arg Arg Leu Arg Phe His His Cys Gly Leu 355 360 365 PheTyr Val Asn Tyr Glu Met Gly Phe Arg Met Ala Ile Thr Ser Phe 370 375 380Leu Tyr Leu Leu Phe Leu Ile Gln Phe Asp Tyr Trp Asn Leu 385 390 395 20320 PRT Drosophila melanogaster 20 Met Val Lys Gln Ala Glu Asp Arg GluHis Gly Ile Met Leu Asp Val 1 5 10 15 Phe Gln Arg Asn Ala Leu Leu TyrGln Ile Ser Ser Leu Met Gly Val 20 25 30 Val Gly Val Val Ser Ile Cys ThrVal His Leu Arg Thr Leu Trp Arg 35 40 45 Ser Lys His Leu Glu Glu Ile TyrAsn Gly Leu Met Leu Leu Glu Ala 50 55 60 Lys Tyr Phe Cys Ser Asn Ala ValGlu Cys Pro Ala Phe Asp Gly Tyr 65 70 75 80 Val Ile Gln Lys Gly Val ValIle Val Val Gly Leu Leu Ala Pro Trp 85 90 95 Met Val His Phe Gly Met ProAsp Ser Lys Leu Pro Val Leu Asn Val 100 105 110 Leu Val Val Ser Met ValLys Leu Gly Thr Leu Leu Leu Ala Leu His 115 120 125 Tyr His Leu Gly ValVal Ile Ile Tyr Arg Phe Val Trp Leu Ile Asn 130 135 140 Arg Glu Leu LeuSer Leu Val Cys Ser Leu Arg Gly Asn His Lys Gly 145 150 155 160 Ser SerSer Arg Val Arg Phe Leu Leu Lys Leu Tyr Asn Lys Leu Val 165 170 175 AsnLeu Tyr Ser Lys Leu Ala Asp Cys Tyr Asp Cys Gln Thr Val Leu 180 185 190Met Met Ala Ile Phe Leu Ala Ala Asn Ile Ile Val Cys Phe Tyr Met 195 200205 Ile Val Tyr Arg Ile Ser Leu Ser Lys Met Ser Phe Phe Val Met Leu 210215 220 Ile Met Phe Pro Leu Ala Ile Ala Asn Asn Phe Met Asp Phe Trp Leu225 230 235 240 Ser Met Lys Val Cys Asp Leu Leu Gln Lys Thr Gly Arg GlnThr Ser 245 250 255 Met Ile Leu Lys Leu Phe Asn Asp Ile Glu Asn Met AspLys Asp Leu 260 265 270 Glu Ile Ser Ile Ser Asp Phe Ala Leu Tyr Cys SerHis Arg Arg Phe 275 280 285 Lys Phe Leu His Cys Gly Leu Phe His Val AsnArg Glu Met Gly Phe 290 295 300 Lys Met Phe Val Ala Ser Val Leu Tyr LeuLeu Tyr Leu Val Gln Phe 305 310 315 320 21 389 PRT Drosophilamelanogaster 21 Met Phe Ala Ser Arg Ser Asp Leu Gln Ser Arg Leu Cys TrpIle Ile 1 5 10 15 Leu Lys Ala Thr Leu Tyr Ser Ser Trp Phe Leu Gly ValPhe Pro Tyr 20 25 30 Arg Phe Asp Ser Arg Asn Gly Gln Leu Lys Arg Ser ArgPhe Leu Leu 35 40 45 Phe Tyr Gly Leu Ile Leu Asn Phe Phe Leu Leu Leu LysMet Val Cys 50 55 60 Ser Gly Gly Gln Lys Leu Gly Ile Pro Glu Ala Phe AlaArg Asn Ser 65 70 75 80 Val Leu Glu Asn Thr His Tyr Thr Thr Gly Met LeuAla Val Phe Ser 85 90 95 Cys Val Val Ile His Phe Leu Asn Phe Trp Gly SerThr Arg Val Gln 100 105 110 Asp Leu Ala Asn Glu Leu Leu Val Leu Glu TyrGln Gln Phe Ala Ser 115 120 125 Leu Asn Glu Thr Lys Cys Pro Lys Phe AsnSer Phe Val Ile Gln Lys 130 135 140 Trp Leu Ser Val Ile Gly Leu Leu LeuSer Tyr Leu Ser Ile Ala Tyr 145 150 155 160 Gly Leu Pro Gly Asn Asn PheSer Val Glu Met Val Leu Ile Asn Ser 165 170 175 Leu Val Gln Phe Ser PheAsn Cys Asn Ile Met His Tyr Tyr Ile Gly 180 185 190 Val Leu Leu Ile TyrArg Tyr Leu Trp Leu Ile Asn Gly Gln Leu Leu 195 200 205 Glu Met Val ThrAsn Leu Lys Leu Asp Cys Ser Val Asp Ser Ser Arg 210 215 220 Ile Arg LysTyr Leu Ser Leu Tyr Arg Arg Leu Leu Glu Leu Lys Gly 225 230 235 240 TyrMet Val Ala Thr Tyr Glu Tyr His Met Thr Leu Val Leu Thr Thr 245 250 255Gly Leu Ala Ser Asn Phe Leu Ala Ile Tyr Ser Trp Ile Val Leu Asp 260 265270 Ile Ser Met Asn Ile Asn Phe Ile Tyr Leu Leu Ile Phe Pro Leu Phe 275280 285 Leu Leu Val Asn Val Trp Asn Leu Trp Leu Ser Ile Ala Ala Ser Asp290 295 300 Leu Ala Glu Asn Ala Gly Lys Ser Thr Gln Thr Val Leu Lys LeuPhe 305 310 315 320 Ala Asp Leu Glu Val Lys Asp Ile Glu Leu Glu Arg SerVal Ser Val 325 330 335 Asn Ser Asn Arg Tyr Lys Gln Val Asn Glu Phe AlaLeu Leu Cys Gly 340 345 350 His Cys Gln Phe Asn Phe His Val Cys Gly LeuPhe Thr Ile Asn Tyr 355 360 365 Lys Met Gly Phe Gln Met Ile Ile Thr SerPhe Leu Tyr Leu Ile Tyr 370 375 380 Met Ile Gln Phe Asp 385 22 287 PRTDrosophila melanogaster 22 Met Ile Asn Val Val Ile Gly Ile Ile Asn ValLeu Ser Ala Leu Ile 1 5 10 15 Val His Phe Met Asn Phe Trp Gly Ser ArgLys Val Gly Glu Ile Cys 20 25 30 Asn Glu Leu Leu Ile Leu Glu Tyr Gln AspPhe Glu Gly Leu Asn Gly 35 40 45 Arg Asn Cys Pro Asn Phe Asn Cys Phe ValIle Gln Lys Cys Leu Thr 50 55 60 Ile Leu Gly Gln Leu Leu Ser Phe Phe ThrLeu Asn Phe Ala Leu Pro 65 70 75 80 Gly Leu Glu Phe His Ile Cys Leu ValLeu Leu Ser Cys Leu Met Glu 85 90 95 Phe Ser Leu Asn Leu Asn Ile Met HisTyr His Val Gly Val Leu Leu 100 105 110 Ile Tyr Arg Tyr Val Trp Leu IleAsn Glu Gln Leu Lys Asp Leu Val 115 120 125 Ser Gln Leu Lys Leu Asn ProGlu Thr Asp Phe Ser Arg Ile His Gln 130 135 140 Phe Leu Ser Leu Tyr LysArg Leu Leu Glu Leu Asn Arg Lys Leu Val 145 150 155 160 Ile Ala Tyr GluTyr Gln Met Thr Leu Phe Ile Ile Ala Gln Leu Ser 165 170 175 Gly Asn IleVal Val Ile Tyr Phe Leu Ile Val Tyr Gly Leu Ser Met 180 185 190 Arg ThrTyr Ser Ile Phe Leu Val Ala Phe Pro Asn Ser Leu Leu Ile 195 200 205 AsnIle Trp Asp Phe Trp Leu Cys Ile Ala Ala Cys Asp Leu Thr Glu 210 215 220Lys Ala Gly Asp Glu Thr Ala Ile Ile Leu Lys Ile Phe Ser Asp Leu 225 230235 240 Glu His Arg Asp Asp Lys Leu Glu Lys Phe Arg Phe Gln Leu Cys Gly245 250 255 Leu Phe Ser Met Asn Cys Arg Met Gly Phe Lys Met Ile Ile ThrThr 260 265 270 Phe Leu Tyr Leu Val Tyr Leu Val Gln Phe Asp Tyr Met AsnLeu 275 280 285 23 410 PRT Drosophila melanogaster 23 Met Ser Gln ProLys Arg Ile His Arg Ile Cys Lys Gly Leu Ala Arg 1 5 10 15 Phe Thr IleArg Ala Thr Leu Tyr Gly Ser Trp Val Leu Gly Leu Phe 20 25 30 Pro Phe ThrPhe Asp Ser Arg Lys Arg Arg Leu Asn Arg Ser Lys Trp 35 40 45 Leu Leu AlaTyr Gly Leu Val Leu Asn Leu Thr Leu Leu Val Leu Ser 50 55 60 Met Leu ProSer Thr Asp Asp His Asn Ser Val Lys Val Glu Val Phe 65 70 75 80 Gln ArgAsn Pro Leu Val Lys Gln Val Glu Glu Leu Val Glu Val Ile 85 90 95 Ser LeuIle Thr Thr Leu Val Thr His Leu Arg Thr Phe Ser Arg Ser 100 105 110 SerGlu Leu Val Glu Ile Leu Asn Glu Leu Leu Val Leu Asp Lys Asn 115 120 125His Phe Ser Lys Leu Met Leu Ser Glu Cys His Thr Phe Asn Arg Tyr 130 135140 Val Ile Glu Lys Gly Leu Val Ile Ile Leu Glu Ile Gly Ser Ser Leu 145150 155 160 Val Leu Tyr Phe Gly Ile Pro Asn Ser Lys Ile Val Val Tyr GluAla 165 170 175 Val Cys Ile Tyr Ile Val Gln Leu Glu Val Leu Met Val ValMet His 180 185 190 Phe His Leu Ala Val Ile Tyr Ile Tyr Arg Tyr Leu TrpIle Ile Asn 195 200 205 Gly Gln Leu Leu Asp Met Ala Ser Arg Leu Arg ArgGly Asp Ser Val 210 215 220 Asp Pro Asp Arg Ile Gln Leu Leu Leu Trp LeuTyr Ser Arg Leu Leu 225 230 235 240 Asp Leu Asn His Arg Leu Thr Ala IleTyr Asp Ile Gln Val Thr Leu 245 250 255 Phe Met Ala Thr Leu Phe Ser ValAsn Ile Ile Val Gly His Val Leu 260 265 270 Val Ile Cys Trp Ile Asn IleThr Arg Phe Ser Leu Leu Val Ile Phe 275 280 285 Leu Leu Phe Pro Gln AlaLeu Ile Ile Asn Phe Trp Asp Leu Trp Gln 290 295 300 Gly Ile Ala Phe CysAsp Leu Ala Glu Ser Thr Gly Lys Lys Thr Ser 305 310 315 320 Met Ile LeuLys Leu Phe Asn Asp Met Glu Asn Met Asp Gln Glu Thr 325 330 335 Glu ArgArg Val Ser Glu Tyr Met Phe Gln Asn Leu Met Tyr Phe Lys 340 345 350 TyrPhe Lys His Pro Leu Ile Phe Val Ala Glu Phe Thr Leu Phe Cys 355 360 365Ser His Arg Arg Leu Lys Val Cys His Leu Gly Leu Leu Asp Ile Asn 370 375380 Tyr Glu Met Gly Phe Arg Met Ile Ile Thr Asn Ile Leu Tyr Val Val 385390 395 400 Phe Leu Val Gln Phe Asp Tyr Met Asn Leu 405 410 24 364 PRTDrosophila melanogaster 24 Met Gly Val Met Pro Ile His Arg Asn Pro ProGlu Lys Asn Leu Pro 1 5 10 15 Arg Thr Gly Tyr Ser Trp Gly Ser Lys GlnVal Met Trp Ala Ile Phe 20 25 30 Ile Tyr Ser Cys Gln Thr Thr Ile Val ValLeu Val Leu Arg Glu Arg 35 40 45 Val Lys Lys Phe Val Thr Ser Pro Asp LysArg Phe Asp Glu Ala Ile 50 55 60 Tyr Asn Val Ile Phe Ile Ser Leu Leu PheThr Asn Phe Leu Leu Pro 65 70 75 80 Val Ala Ser Trp Arg His Gly Pro GlnVal Ala Ile Phe Lys Asn Met 85 90 95 Trp Thr Asn Tyr Gln Tyr Lys Phe PheLys Thr Thr Gly Ser Pro Ile 100 105 110 Val Phe Pro Asn Leu Tyr Pro LeuThr Trp Ser Leu Cys Val Phe Ser 115 120 125 Trp Leu Leu Ser Ile Ala IleAsn Leu Ser Gln Tyr Phe Leu Gln Pro 130 135 140 Asp Phe Arg Leu Trp TyrThr Phe Ala Tyr Tyr Pro Ile Ile Ala Met 145 150 155 160 Leu Asn Cys PheCys Ser Leu Trp Tyr Ile Asn Cys Asn Ala Phe Gly 165 170 175 Thr Ala SerArg Ala Leu Ser Asp Ala Leu Gln Thr Thr Ile Arg Gly 180 185 190 Glu LysPro Ala Gln Lys Leu Thr Glu Tyr Arg His Leu Trp Val Asp 195 200 205 LeuSer His Met Met Gln Gln Leu Gly Arg Ala Tyr Ser Asn Met Tyr 210 215 220Gly Met Tyr Cys Leu Val Ile Phe Phe Thr Thr Ile Ile Ala Thr Tyr 225 230235 240 Gly Ser Ile Ser Glu Ile Ile Asp His Gly Ala Thr Tyr Lys Glu Val245 250 255 Gly Leu Phe Val Ile Val Phe Tyr Cys Met Gly Leu Leu Tyr IleIle 260 265 270 Cys Asn Glu Ala His Tyr Ala Ser Arg Lys Val Gly Leu AspPhe Gln 275 280 285 Thr Lys Leu Leu Asn Ile Asn Leu Thr Ala Val Asp AlaAla Thr Gln 290 295 300 Lys Glu Val Glu Met Leu Leu Val Ala Ile Asn LysAsn Pro Pro Ile 305 310 315 320 Met Asn Leu Asp Gly Tyr Ala Asn Ile AsnArg Glu Leu Ile Thr Thr 325 330 335 Asn Ile Ser Phe Met Ala Thr Tyr LeuVal Val Leu Leu Gln Phe Lys 340 345 350 Ile Thr Glu Gln Arg Arg Ile GlyGln Gln Gln Ala 355 360 25 377 PRT Drosophila melanogaster 25 Met PheGln Pro Arg Arg Gly Phe Ser Cys His Leu Ala Trp Phe Met 1 5 10 15 LeuGln Thr Thr Leu Tyr Ala Ser Trp Leu Leu Gly Leu Phe Pro Phe 20 25 30 ThrPhe Asp Ser Arg Arg Lys Gln Leu Lys Arg Ser Arg Trp Leu Leu 35 40 45 LeuTyr Gly Phe Val Leu His Ser Leu Ala Met Cys Leu Ala Met Ser 50 55 60 SerHis Leu Ala Ser Lys Gln Arg Arg Lys Tyr Asn Ala Phe Glu Arg 65 70 75 80Asn Pro Leu Leu Glu Lys Ile Tyr Met Gln Phe Gln Val Thr Thr Phe 85 90 95Phe Thr Ile Ser Val Leu Leu Leu Met Asn Val Trp Lys Ser Asn Thr 100 105110 Val Arg Lys Ile Ala Asn Glu Leu Leu Thr Leu Glu Gly Gln Val Lys 115120 125 Asp Leu Leu Thr Leu Lys Asn Cys Pro Asn Phe Asn Cys Phe Val Ile130 135 140 Lys Lys His Val Ala Ala Ile Gly Gln Phe Val Ile Ser Ile TyrPhe 145 150 155 160 Cys Leu Cys Gln Glu Asn Ser Tyr Pro Lys Ile Leu LysIle Leu Cys 165 170 175 Cys Leu Pro Ser Val Gly Leu Gln Leu Ile Ile MetHis Phe His Thr 180 185 190 Glu Ile Ile Leu Val Tyr Arg Tyr Val Trp LeuVal Asn Glu Thr Leu 195 200 205 Glu Asp Ser His His Leu Ser Ser Ser ArgIle His Ala Leu Ala Ser 210 215 220 Leu Tyr Asp Arg Leu Leu Lys Leu SerGlu Leu Val Val Ala Cys Asn 225 230 235 240 Asp Leu Gln Leu Ile Leu MetLeu Ile Ile Tyr Leu Ile Gly Asn Thr 245 250 255 Val Gln Ile Phe Phe LeuIle Val Leu Gly Val Ser Met Asn Lys Arg 260 265 270 Tyr Ile Tyr Leu ValAla Ser Pro Gln Leu Ile Ile Asn Phe Trp Asp 275 280 285 Phe Trp Leu AsnIle Val Val Cys Asp Leu Ala Gly Lys Cys Gly Asp 290 295 300 Gln Thr SerLys Val Leu Lys Leu Phe Thr Asp Leu Glu His Asp Asp 305 310 315 320 GluGlu Leu Glu Arg Ser Leu Asn Glu Phe Ala Trp Leu Cys Thr His 325 330 335Arg Lys Phe Arg Phe Gln Leu Cys Gly Leu Phe Ser Ile Asn His Asn 340 345350 Met Gly Phe Gln Met Ile Ile Thr Ser Phe Leu Tyr Leu Val Tyr Leu 355360 365 Leu Gln Phe Asp Phe Met Asn Leu Cys 370 375 26 370 PRTDrosophila melanogaster 26 Met Lys Thr Leu Glu Cys Leu Thr Arg Arg PheLeu Glu Val Ile Phe 1 5 10 15 Ser Val Leu Ala Leu Val Pro Leu Pro ProIle Ser Gln Leu Gly Trp 20 25 30 Leu Phe Leu Ser Leu Ala Ile Arg Cys CysTrp Ile Val Tyr Phe Ile 35 40 45 Tyr Leu Leu Asp Val Ala Ile Ser Phe SerTrp Val Ala Ile Glu Asn 50 55 60 Val Gly Asn Ala Val Gly Thr Met Leu PheVal Gly Asn Ser Val Leu 65 70 75 80 Gly Phe Ala Leu Leu Leu Glu Ser ValLeu Lys Gln Lys Thr His Ser 85 90 95 Gln Leu Glu Asp Leu Arg Val Gln ThrGlu Leu Gln Leu Gln Arg Leu 100 105 110 Gly Met Phe Gly Arg Ser Arg HisAla Ala Tyr Leu Leu Pro Leu Ile 115 120 125 Gly Val Gln Phe Thr Cys AspLeu Val Arg Leu Ala Thr Asn Phe Gly 130 135 140 Glu Thr Val Ser Pro ValPhe Cys Ile Ser Leu Pro Leu Met Trp Leu 145 150 155 160 Leu Arg Tyr ArgTyr Val Gln Leu Val Gln His Val Met Asp Leu Asn 165 170 175 Gln Arg SerIle His Leu Arg Arg Ser Leu Leu Ser Met Ala Ser Gly 180 185 190 Asn AspLeu Trp Gln Pro Tyr Gly Val Gln Glu Cys Leu Gln Leu Gln 195 200 205 ThrLeu Arg Thr Thr Tyr Glu Arg Ile Phe Glu Cys Tyr Glu Thr Phe 210 215 220Ser Asp Cys Tyr Gly Trp Gly Met Leu Gly Leu His Leu Leu Thr Ser 225 230235 240 Phe Gln Phe Val Thr Asn Ala Tyr Trp Met Ile Met Gly Ile Tyr Asp245 250 255 Gly Gly Asn Val Arg Ser Leu Ile Phe Asn Gly Ala Thr Gly IleAsp 260 265 270 Phe Gly Thr Pro Ile Ala Thr Leu Phe Trp His Gly Asp SerGly Ala 275 280 285 Glu Asn Gly Arg Gln Ile Gly Cys Leu Ile Ser Lys LeuVal Lys Pro 290 295 300 Gln Gly Ser Lys Leu Tyr Asn Asp Leu Val Ser GluPhe Ser Leu Gln 305 310 315 320 Thr Leu His Gln Arg Phe Val Val Thr AlaLys Asp Phe Phe Ser Leu 325 330 335 Asn Leu His Leu Leu Ser Ser Met PheAla Ala Val Val Thr Tyr Leu 340 345 350 Val Ile Leu Ile Gln Phe Met PheAla Glu Arg Ser Ser Thr Arg Gly 355 360 365 Ser Gly 370 27 374 PRTDrosophila melanogaster 27 Met Phe Pro Pro Thr Arg Val Gln Ala Ser SerArg Val Val Leu Lys 1 5 10 15 Ile Phe His Phe Ile Leu Val Ala Phe SerLeu Arg Ser Arg Arg Leu 20 25 30 Ser Arg Leu Val Leu Trp Leu Gln Phe LeuGly Trp Leu Thr Trp Phe 35 40 45 Ile Ser Met Trp Thr Gln Ser Val Ile TyrAla Gln Thr Ile Asp Cys 50 55 60 Thr Leu Asp Cys Ser Leu Arg His Ile LeuThr Phe Phe Gln Thr Val 65 70 75 80 Ser His Ala Phe Ile Val Val Thr SerPhe Leu Asp Gly Phe Arg Ile 85 90 95 Lys Gln Asp Gln Leu Asp Glu Pro IleAla Phe Glu Asp Ser Asp Pro 100 105 110 Trp Leu Ala Phe Thr Val Leu AlaMet Leu Val Pro Thr Leu Gly Val 115 120 125 Glu Tyr Leu Val Cys Ser AsnAla Pro Glu Tyr Ala Phe Arg Ile Arg 130 135 140 Ile Tyr His Leu Lys ThrLeu Pro Ser Phe Leu Ala Leu Gln Val Gln 145 150 155 160 Ile Ile Ser PheIle Leu Glu Val Met Lys Val Asn Ile Arg Val Arg 165 170 175 Gln Thr LysLeu Gln Leu Leu Ile Leu Ala Arg Glu Leu Ser Cys Arg 180 185 190 Trp ProGln Arg Lys Gln Lys Pro Gln Phe Ser Asp Gln Gln Ala His 195 200 205 ArgVal Lys Asp Leu Lys Arg Arg Tyr Asn Asp Leu His Tyr Leu Phe 210 215 220Val Arg Ile Asn Gly Tyr Phe Gly Gly Ser Leu Leu Thr Ile Ile Ile 225 230235 240 Val His Phe Ala Ile Phe Val Ser Asn Ser Tyr Trp Leu Phe Val Asp245 250 255 Ile Arg Thr Arg Pro Trp Arg Ile Tyr Ala Ile Leu Leu Asn LeuGly 260 265 270 Phe Ile Phe Asn Val Ala Leu Gln Met Ala Ala Ala Cys TrpHis Cys 275 280 285 Gln Gln Ser Tyr Asn Leu Gly Arg Gln Ile Gly Cys LeuIle Ser Lys 290 295 300 Leu Val Lys Pro Gln Gly Ser Lys Leu Tyr Asn AspLeu Val Ser Glu 305 310 315 320 Phe Ser Leu Gln Thr Leu His Gln Arg PheVal Val Thr Ala Lys Asp 325 330 335 Phe Phe Ser Leu Asn Leu His Leu LeuSer Ser Met Phe Ala Ala Val 340 345 350 Val Thr Tyr Leu Val Ile Leu IleGln Phe Met Phe Ala Glu Arg Ser 355 360 365 Ser Thr Arg Gly Ser Gly 37028 416 PRT Drosophila melanogaster 28 Met Pro Ile Tyr Glu Gln Val SerAsp Tyr Glu Val Gly Pro Pro Thr 1 5 10 15 Lys Thr Asn Glu Phe Tyr SerPhe Phe Val Arg Gly Val Val His Ala 20 25 30 Leu Thr Ile Phe Asn Val TyrSer Leu Phe Thr Pro Ile Ser Ala Gln 35 40 45 Leu Phe Phe Ser Tyr Arg GluThr Asp Asn Val Asn Gln Trp Ile Glu 50 55 60 Leu Leu Leu Cys Ile Leu ThrTyr Thr Leu Thr Val Phe Val Cys Ala 65 70 75 80 His Asn Thr Thr Ser MetLeu Arg Ile Met Asn Glu Ile Leu Gln Leu 85 90 95 Asp Glu Glu Val Arg ArgGln Phe Gly Ala Asn Leu Ser Gln Asn Phe 100 105 110 Gly Phe Leu Val LysPhe Leu Val Gly Ile Thr Ala Cys Gln Ala Tyr 115 120 125 Ile Ile Val LeuLys Ile Tyr Ala Val Gln Gly Glu Ile Thr Pro Thr 130 135 140 Ser Tyr IleLeu Leu Ala Phe Tyr Gly Ile Gln Asn Gly Leu Thr Ala 145 150 155 160 ThrTyr Ile Val Phe Ala Ser Ala Leu Leu Arg Ile Val Tyr Ile Arg 165 170 175Phe His Phe Ile Asn Gln Leu Leu Asn Gly Tyr Thr Tyr Gly Gln Gln 180 185190 His Arg Arg Lys Glu Gly Gly Ala Arg Ala Arg Arg Gln Arg Gly Asp 195200 205 Val Asn Pro Asn Val Asn Pro Ala Leu Met Glu His Phe Pro Glu Asp210 215 220 Ser Leu Phe Ile Tyr Arg Met His Asn Lys Leu Leu Arg Ile TyrLys 225 230 235 240 Gly Ile Asn Asp Cys Cys Asn Leu Ile Leu Val Ser PheLeu Gly Tyr 245 250 255 Ser Phe Tyr Thr Val Thr Thr Asn Cys Tyr Asn LeuPhe Val Gln Ile 260 265 270 Thr Gly Lys Gly Met Val Ser Pro Asn Ile LeuGln Trp Cys Phe Ala 275 280 285 Trp Leu Cys Leu His Val Ser Leu Leu AlaLeu Leu Ser Arg Ser Cys 290 295 300 Gly Leu Thr Thr Thr Glu Val Ser AsnTyr Ile Gly Asp Lys Ile Ser 305 310 315 320 Ile Phe Met Ser Val Phe IleSer Arg Pro Met Pro His Pro Lys Phe 325 330 335 Leu Gln Gly Cys Met ProSer Arg Arg Ser Ile Arg Ile Ser Gly Phe 340 345 350 His Tyr Gln Ile AspLys Phe Leu Thr Lys Ser Ile Lys Gln Glu Val 355 360 365 Gln Phe Thr AlaTyr Gly Phe Phe Ala Ile Asp Asn Ser Thr Leu Phe 370 375 380 Lys Ile PheSer Ala Val Thr Thr Tyr Leu Val Ile Leu Ile Gln Phe 385 390 395 400 LysGln Leu Glu Asp Ser Lys Val Glu Asp Pro Val Pro Glu Gln Thr 405 410 41529 369 PRT Drosophila melanogaster 29 Met Leu Tyr Ser Phe His Pro TyrLeu Lys Tyr Phe Ala Leu Leu Gly 1 5 10 15 Leu Val Pro Trp Ser Glu SerCys Ala Gln Ser Lys Phe Val Gln Lys 20 25 30 Val Tyr Ser Ala Ile Leu IleIle Leu Asn Ala Val His Phe Gly Ile 35 40 45 Ser Ile Tyr Phe Pro Gln SerAla Glu Leu Phe Leu Ser Leu Met Val 50 55 60 Asn Val Ile Val Phe Val AlaArg Ile Val Cys Val Thr Val Ile Ile 65 70 75 80 Leu Gln Val Met Val HisTyr Asp Asp Tyr Phe Arg Phe Cys Arg Glu 85 90 95 Met Lys Tyr Leu Gly LeuArg Leu Gln Cys Glu Leu Lys Ile His Val 100 105 110 Gly Arg Leu Lys TrpGln Ser Tyr Ala Lys Ile Leu Ala Leu Gly Ile 115 120 125 Gly Phe Leu ValThr Val Leu Pro Ser Ile Tyr Val Ala Leu Ser Gly 130 135 140 Ser Leu LeuTyr Phe Trp Ser Ser Leu Leu Ser Ile Leu Ile Ile Arg 145 150 155 160 MetGln Phe Val Leu Val Leu Leu Asn Val Glu Leu Leu Gly His His 165 170 175Val Ser Leu Leu Gly Ile Arg Leu Gln Asn Val Leu Glu Cys His Leu 180 185190 Met Gly Ala Asn Cys Thr Leu Asp Gly Asn Ala Asn Arg Leu Cys Ser 195200 205 Leu Glu Phe Leu Leu Ala Leu Lys Gln Ser His Met Gln Leu His Tyr210 215 220 Leu Phe Thr His Phe Asn Asp Leu Phe Gly Trp Ser Ile Leu GlyThr 225 230 235 240 Tyr Val Val Leu Phe Ser Asp Ser Thr Val Asn Ile TyrTrp Thr Gln 245 250 255 Gln Val Leu Val Glu Val Tyr Glu Tyr Lys Tyr LeuTyr Ala Thr Phe 260 265 270 Ser Val Phe Val Pro Ser Phe Phe Asn Ile LeuVal Phe Cys Arg Cys 275 280 285 Gly Glu Phe Cys Gln Arg Gln Ser Val LeuIle Gly Ser Tyr Leu Arg 290 295 300 Asn Leu Ser Cys His Pro Ser Ile GlyArg Glu Thr Ser Tyr Lys Asp 305 310 315 320 Leu Leu Met Glu Phe Ile LeuGln Val Glu Gln Asn Val Leu Ala Ile 325 330 335 Asn Ala Glu Gly Phe MetSer Thr Asp Asn Ser Leu Leu Met Ser Ile 340 345 350 Leu Ala Ala Lys ValThr Tyr Leu Ile Val Leu Met Gln Phe Ser Ser 355 360 365 Val 30 372 PRTDrosophila melanogaster 30 Met Gly Thr Arg Asn Arg Lys Leu Leu Phe PheLeu His Tyr Gln Arg 1 5 10 15 Tyr Leu Gly Leu Thr Asn Leu Asp Phe SerLys Ser Leu His Ile Tyr 20 25 30 Trp Leu His Gly Thr Trp Ser Ser Thr AlaIle Gln Ile Val Val Val 35 40 45 Gly Val Phe Met Ala Ala Leu Leu Gly AlaLeu Ala Glu Ser Leu Tyr 50 55 60 Tyr Met Glu Thr Lys Ser Gln Thr Gly AsnThr Phe Asp Asn Ala Val 65 70 75 80 Ile Leu Thr Thr Ser Val Thr Gln LeuLeu Ala Asn Leu Trp Leu Arg 85 90 95 Ser Gln Gln Lys Ser Gln Val Asn LeuLeu Gln Arg Leu Ser Gln Val 100 105 110 Val Glu Leu Leu Gln Phe Glu ProTyr Ala Val Pro Gln Phe Arg Trp 115 120 125 Leu Tyr Arg Ile Trp Leu LeuVal Cys Leu Ile Tyr Gly Ala Met Val 130 135 140 Thr His Phe Gly Ile AsnTrp Leu Thr Thr Met Gln Ile Ser Arg Val 145 150 155 160 Leu Thr Leu IleGly Phe Val Tyr Arg Cys Val Leu Ala Asn Phe Gln 165 170 175 Phe Thr CysTyr Thr Gly Met Val Val Ile Leu Lys Lys Leu Leu Gln 180 185 190 Val GlnVal Lys Gln Leu Glu His Leu Val Ser Thr Thr Thr Ile Ser 195 200 205 MetAla Gly Val Ala Gly Cys Leu Arg Thr His Asp Glu Ile Leu Leu 210 215 220Leu Gly Gln Arg Glu Leu Ile Ala Val Tyr Gly Gly Val Ile Leu Phe 225 230235 240 Leu Phe Ile Tyr Gln Val Met Gln Cys Ile Leu Ile Phe Tyr Ile Ser245 250 255 Asn Leu Glu Gly Phe His Ser Ser Asn Asp Leu Val Leu Ile PheCys 260 265 270 Trp Leu Ala Pro Met Leu Phe Tyr Leu Ile Leu Pro Leu ValVal Asn 275 280 285 Asp Ile His Asn Gln Ala Asn Lys Thr Ala Lys Met LeuThr Lys Val 290 295 300 Pro Arg Thr Gly Thr Gly Leu Asp Arg Met Ile GluLys Phe Leu Leu 305 310 315 320 Lys Asn Leu Arg Gln Lys Pro Ile Leu ThrAla Tyr Gly Phe Phe Ala 325 330 335 Leu Asp Lys Ser Thr Leu Phe Lys LeuPhe Thr Ala Ile Phe Thr Tyr 340 345 350 Met Val Ile Leu Val Gln Phe LysGlu Met Glu Asn Ser Thr Lys Ser 355 360 365 Ile Asn Lys Phe 370 31 381PRT Drosophila melanogaster 31 Met Asp Phe Gln Pro Gly Glu Leu Cys AlaTyr Tyr Arg Leu Cys Arg 1 5 10 15 Tyr Leu Gly Ile Phe Cys Ile Asp TyrAsn Pro Thr Lys Lys Lys Phe 20 25 30 Arg Leu Arg Arg Ser Val Leu Cys TyrIle Val His Phe Ala Leu Gln 35 40 45 Ala Tyr Leu Val Gly Cys Ile Ser ValMet Val Thr Tyr Trp Arg Arg 50 55 60 Cys Phe Lys Ser Glu Leu Thr Thr ThrGly Asn His Phe Asp Arg Leu 65 70 75 80 Val Met Val Ile Ala Leu Gly IleLeu Val Val Gln Asn Ala Trp Leu 85 90 95 Ile Trp Leu Gln Ala Pro His LeuArg Ile Val Arg Gln Ile Glu Phe 100 105 110 Tyr Arg Arg Asn His Leu AlaAsn Val Arg Leu Leu Leu Pro Lys Arg 115 120 125 Leu Leu Trp Leu Ile IleAla Thr Asn Val Val Tyr Met Ala Asn Phe 130 135 140 Ile Lys Thr Cys IlePhe Glu Trp Leu Thr Asp Ala Ser Arg Leu Phe 145 150 155 160 Val Ile ThrSer Leu Gly Phe Pro Leu Arg Tyr Leu Val Thr Ser Phe 165 170 175 Thr MetGly Thr Tyr Phe Cys Met Val His Ile Val Arg Leu Val Leu 180 185 190 AspTrp Asn Gln Ser Gln Ile Asn Ala Ile Ile Asp Glu Ser Ala Asp 195 200 205Leu Lys Met Thr Ser Pro Asn Arg Leu Arg Leu Arg Val Cys Leu Glu 210 215220 Met His Asp Arg Leu Met Leu Leu Cys Asn Asp Glu Ile Ser Leu Val 225230 235 240 Tyr Gly Phe Ile Ala Trp Leu Ser Trp Met Phe Ala Ser Leu AspVal 245 250 255 Thr Gly Val Ile Tyr Leu Thr Met Val Ile Gln Thr Lys LysSer Ile 260 265 270 Val Leu Lys Leu Ile Thr Asn Val Val Trp Leu Ser ProThr Phe Met 275 280 285 Thr Cys Ala Ala Ser Phe Met Ser Asn Arg Val ThrIle Gln Ala Asn 290 295 300 Lys Thr Ala Lys Met Leu Thr Lys Val Pro ArgThr Gly Thr Gly Leu 305 310 315 320 Asp Arg Met Ile Glu Lys Phe Leu LeuLys Asn Leu Arg Gln Lys Pro 325 330 335 Ile Leu Thr Ala Tyr Gly Phe PheAla Leu Asp Lys Ser Thr Leu Phe 340 345 350 Lys Leu Phe Thr Ala Ile PheThr Tyr Met Val Ile Leu Val Gln Phe 355 360 365 Lys Glu Met Glu Asn SerThr Lys Ser Ile Asn Lys Phe 370 375 380 32 381 PRT Drosophilamelanogaster 32 Met Lys Arg Asn Ala Phe Glu Glu Leu Arg Val Gln Leu ArgThr Leu 1 5 10 15 Lys Trp Leu Gly Val Leu Arg Phe Thr Ile Asp Phe AsnLys Cys Leu 20 25 30 Val Arg Glu Asn Ala Ser Glu Glu Arg Ser Ala Trp LeuTyr Leu Ile 35 40 45 Gly Val Val Gly Ile Thr Cys Ser Leu Ile Val Tyr SerThr Tyr Phe 50 55 60 Pro Ser His Phe Ile Met Gly Lys His Asn Thr Thr GlyAsn Cys Tyr 65 70 75 80 Ala Leu Ile Asn Ile Arg Ser Cys Ser Ile Val ThrMet Leu Ile Tyr 85 90 95 Thr Gln Leu Tyr Ile Gln Arg Phe Arg Phe Val AlaLeu Leu Gln Ser 100 105 110 Ile Leu Arg Phe Asn Gln Ile Ser Gly Ser HisArg Glu Glu Gly Arg 115 120 125 Phe Ala Phe Tyr Tyr Tyr Thr His Leu SerLeu Leu Ile Ile Cys Met 130 135 140 Leu Asn Tyr Ala Tyr Gly Tyr Trp ThrAla Gly Val Arg Leu Thr Thr 145 150 155 160 Ile Pro Ile Tyr Leu Leu GlnTyr Gly Phe Ser Tyr Leu Phe Leu Gly 165 170 175 Gln Val Val Val Leu PheAla Cys Ile Gln Gln Ile Leu Leu Ser Ile 180 185 190 Leu Lys Tyr Tyr AsnGln Val Val Leu Lys Asn Ile Lys Ser Ser Lys 195 200 205 Glu Ser Arg GluPhe Tyr Tyr Asn Phe Cys Lys Tyr Asn Gln Val Ile 210 215 220 Trp Leu SerTyr Thr Glu Ile Asn His Cys Phe Gly Leu Leu Leu Leu 225 230 235 240 LeuVal Thr Gly Leu Ile Leu Leu Ile Thr Pro Ser Gly Pro Phe Tyr 245 250 255Leu Val Ser Thr Ile Phe Glu Gly Arg Phe Arg Gln Asn Trp Gln Phe 260 265270 Ser Leu Met Ser Phe Thr Ala Ile Leu Trp Ser Leu Pro Trp Ile Val 275280 285 Leu Leu Val Leu Ala Met Gly Arg Asn Asp Val Gln Lys Glu Ala Asn290 295 300 Lys Thr Ala Lys Met Leu Thr Lys Val Pro Arg Thr Gly Thr GlyLeu 305 310 315 320 Asp Arg Met Ile Glu Lys Phe Leu Leu Lys Asn Leu ArgGln Lys Pro 325 330 335 Ile Leu Thr Ala Tyr Gly Phe Phe Ala Leu Asp LysSer Thr Leu Phe 340 345 350 Lys Leu Phe Thr Ala Ile Phe Thr Tyr Met ValIle Leu Val Gln Phe 355 360 365 Lys Glu Met Glu Asn Ser Thr Lys Ser IleAsn Lys Phe 370 375 380 33 371 PRT Drosophila melanogaster 33 Met SerLys Val Cys Arg Asp Leu Arg Ile Tyr Leu Arg Leu Leu His 1 5 10 15 IleMet Gly Met Met Cys Trp His Phe Asp Ser Asp His Cys Gln Leu 20 25 30 ValAla Thr Ser Gly Ser Glu Arg Tyr Ala Val Val Tyr Ala Gly Cys 35 40 45 IleLeu Val Ser Thr Thr Ala Gly Phe Ile Phe Ala Leu Leu His Pro 50 55 60 SerArg Phe His Ile Ala Ile Tyr Asn Gln Thr Gly Asn Phe Tyr Glu 65 70 75 80Ala Val Ile Phe Arg Ser Thr Cys Val Val Leu Phe Leu Val Tyr Val 85 90 95Ile Leu Tyr Ala Trp Arg His Arg Tyr Arg Asp Leu Val Gln His Ile 100 105110 Leu Arg Leu Asn Arg Arg Cys Ala Ser Ser Cys Thr Asn Gln Gln Phe 115120 125 Leu His Asn Ile Ile Leu Tyr Gly Met Leu Thr Ile Leu Cys Phe Gly130 135 140 Asn Tyr Leu His Gly Tyr Thr Arg Ala Gly Leu Ala Thr Leu ProLeu 145 150 155 160 Ala Leu Cys Met Leu Val Tyr Ile Phe Ala Phe Leu ValLeu Cys Leu 165 170 175 Leu Leu Met Phe Phe Val Ser Leu Lys Gln Val MetThr Ala Gly Leu 180 185 190 Ile His Tyr Asn Gln Gln Leu Cys Gln Gly AspLeu Ile Ser Gly Leu 195 200 205 Arg Gly Arg Gln Gln Ile Leu Lys Leu CysGly Gly Glu Leu Asn Glu 210 215 220 Cys Phe Gly Leu Leu Met Leu Pro IleVal Ala Leu Val Leu Leu Met 225 230 235 240 Ala Pro Ser Gly Pro Phe PheLeu Ile Ser Thr Val Leu Glu Gly Lys 245 250 255 Phe Arg Pro Asp Glu CysLeu Ile Met Leu Leu Thr Ser Ser Thr Trp 260 265 270 Asp Thr Pro Trp MetIle Met Leu Val Leu Met Leu Arg Thr Asn Gly 275 280 285 Ile Ser Glu GluAla Asn Lys Thr Ala Lys Met Leu Thr Lys Val Pro 290 295 300 Arg Thr GlyThr Gly Leu Asp Arg Met Ile Glu Lys Phe Leu Leu Lys 305 310 315 320 AsnLeu Arg Gln Lys Pro Ile Leu Thr Ala Tyr Gly Phe Phe Ala Leu 325 330 335Asp Lys Ser Thr Leu Phe Lys Leu Phe Thr Ala Ile Phe Thr Tyr Met 340 345350 Val Ile Leu Val Gln Phe Lys Glu Met Glu Asn Ser Thr Lys Ser Ile 355360 365 Asn Lys Phe 370 34 379 PRT Drosophila melanogaster 34 Met LysSer Ala Thr Ser Lys Val Val Thr Ala Leu Asp Val Ser Val 1 5 10 15 ValVal Met Ala Ile Val Ser Gly Val Tyr Cys Gly Leu Phe Ser Leu 20 25 30 AsnAsp Thr Leu Glu Leu Asn Asp Arg Leu Asn Lys Ile Asp Asn Thr 35 40 45 LeuAsn Ala Tyr Asn Asn Phe Arg Arg Asp Arg Trp Arg Ala Leu Gly 50 55 60 MetAla Ala Val Ser Leu Leu Ala Ile Ser Ile Leu Val Gly Leu Asp 65 70 75 80Val Gly Thr Trp Met Arg Ile Ala Gln Asp Met Asn Ile Ala Gln Ser 85 90 95Asp Thr Glu Leu Asn Val His Trp Tyr Ile Pro Phe Tyr Ser Leu Tyr 100 105110 Phe Ile Leu Thr Gly Leu Gln Val Asn Ile Ala Asn Thr Ala Tyr Gly 115120 125 Leu Gly Arg Arg Phe Gly Arg Leu Asn Arg Met Leu Ser Ser Ser Phe130 135 140 Leu Ala Glu Asn Asn Ala Thr Ser Ala Ile Lys Pro Gln Lys ValSer 145 150 155 160 Thr Val Lys Asn Val Ser Val Asn Arg Pro Ala Met ProSer Ala Leu 165 170 175 His Ala Ser Leu Thr Lys Leu Asn Gly Glu Thr LeuPro Ser Glu Ala 180 185 190 Ala Gly Asp Lys Ala Ala Ala Arg Ser Leu IleLeu Asn Val Glu Leu 195 200 205 Leu Lys Leu Gly Tyr Phe Pro Ala Lys AsnLys Gly Leu Leu Leu Lys 210 215 220 Ser Leu Ala Asp Ser His Glu Ser LeuGly Lys Cys Val His Leu Leu 225 230 235 240 Ser Asn Ser Phe Gly Ile AlaVal Leu Phe Ile Leu Val Ser Cys Leu 245 250 255 Leu His Leu Val Ala ThrAla Tyr Phe Leu Phe Leu Glu Leu Leu Ser 260 265 270 Lys Arg Asp Asn GlyTyr Leu Trp Val Gln Met Leu Trp Ile Cys Phe 275 280 285 His Phe Leu ArgLeu Leu Met Val Val Glu Pro Cys His Leu Ala Ala 290 295 300 Arg Glu SerArg Lys Thr Ile Gln Ile Val Cys Glu Ile Glu Arg Lys 305 310 315 320 ValHis Glu Pro Ile Leu Ala Glu Ala Val Lys Lys Phe Trp Gln Gln 325 330 335Leu Leu Val Val Asp Ala Asp Phe Ser Ala Cys Gly Leu Cys Arg Val 340 345350 Asn Arg Thr Ile Leu Thr Ser Phe Ala Ser Ala Ile Ala Thr Tyr Leu 355360 365 Val Ile Leu Ile Gln Phe Gln Arg Thr Asn Gly 370 375 35 361 PRTDrosophila melanogaster 35 Met Ala Phe Thr Ser Ser Gln Leu Cys Ser LeuLeu Thr Lys Phe Thr 1 5 10 15 Ala Leu Asn Gly Leu Asn Thr Tyr Tyr PheAsp Thr Lys Thr Asn Ala 20 25 30 Phe Arg Val Ser Ser Lys Leu Lys Ile TyrCys Ala Ile His His Ala 35 40 45 Leu Cys Val Leu Ala Leu Ala His Met SerTyr Ser Thr Ala Ser Asn 50 55 60 Leu Arg Val Ser Val Thr Val Leu Thr IleGly Gly Thr Met Ala Cys 65 70 75 80 Cys Val Lys Ser Cys Trp Glu Lys AlaGln Gly Ile Arg Asn Leu Ala 85 90 95 Arg Gly Leu Val Thr Met Glu Gln LysTyr Phe Ala Gly Arg Pro Ser 100 105 110 Gly Leu Leu Leu Lys Cys Arg TyrTyr Ile Lys Ile Thr Phe Gly Ser 115 120 125 Ile Thr Leu Leu Arg Ile HisLeu Ile Gln Pro Ile Tyr Met Arg Arg 130 135 140 Leu Leu Pro Ser Gln PheTyr Leu Asn Val Gly Ala Tyr Trp Leu Leu 145 150 155 160 Tyr Asn Met LeuLeu Ala Ala Val Leu Gly Phe Tyr Phe Leu Leu Trp 165 170 175 Glu Met CysArg Ile Gln Lys Leu Ile Asn Asp Gln Met Thr Leu Ile 180 185 190 Leu AlaArg Ser Gly Gln Arg Asn Arg Leu Lys Lys Met Gln His Cys 195 200 205 LeuArg Leu Tyr Ser Lys Leu Leu Leu Leu Cys Asp Gln Phe Asn Ser 210 215 220Gln Leu Gly His Val Ala Ile Trp Val Leu Ala Cys Lys Ser Trp Cys 225 230235 240 Gln Ile Thr Phe Gly Tyr Glu Ile Phe Gln Met Val Ala Ala Pro Lys245 250 255 Ser Ile Asp Leu Thr Met Ser Met Arg Val Phe Val Ile Phe ThrTyr 260 265 270 Ile Phe Asp Ala Met Asn Leu Phe Leu Gly Thr Asp Ile SerGlu Leu 275 280 285 Phe Ser Thr Phe Arg Ala Asp Ser Gln Arg Ile Leu ArgGlu Thr Ser 290 295 300 Arg Leu Asp Arg Leu Leu Ser Met Phe Ala Leu LysLeu Ala Leu His 305 310 315 320 Pro Lys Arg Val Val Leu Leu Asn Val PheThr Phe Asp Arg Lys Leu 325 330 335 Thr Leu Thr Leu Leu Ala Lys Ser ThrLeu Tyr Thr Ile Cys Cys Leu 340 345 350 Gln Asn Asp Tyr Asn Lys Leu LysAla 355 360 36 395 PRT Drosophila melanogaster 36 Met Leu Leu Lys PheMet Tyr Ile Tyr Gly Ile Gly Cys Gly Leu Met 1 5 10 15 Pro Ala Pro LeuLys Lys Gly Gln Phe Leu Leu Gly Tyr Lys Gln Arg 20 25 30 Trp Tyr Leu IleTyr Thr Ala Cys Leu His Gly Gly Leu Leu Thr Val 35 40 45 Leu Pro Phe ThrPhe Pro His Tyr Met Tyr Asp Asp Ser Tyr Met Ser 50 55 60 Ser Asn Pro ValLeu Lys Trp Thr Phe Asn Leu Thr Asn Ile Thr Arg 65 70 75 80 Ile Met AlaMet Phe Ser Gly Val Leu Leu Met Trp Phe Arg Arg Lys 85 90 95 Arg Ile LeuAsn Leu Gly Glu Asn Leu Ile Leu His Cys Leu Lys Cys 100 105 110 Lys ThrLeu Asp Asn Arg Ser Lys Lys Tyr Ser Lys Leu Arg Lys Arg 115 120 125 ValArg Asn Val Leu Phe Gln Met Leu Leu Val Ala Asn Leu Ser Ile 130 135 140Leu Leu Gly Ala Leu Ile Leu Phe Arg Ile His Ser Val Gln Arg Ile 145 150155 160 Ser Lys Thr Ala Met Ile Val Ala His Ile Thr Gln Phe Ile Tyr Val165 170 175 Val Phe Met Met Thr Gly Ile Cys Val Ile Leu Leu Val Leu HisTrp 180 185 190 Gln Ser Glu Arg Leu Gln Ile Ala Leu Lys Asp Leu Cys SerPhe Leu 195 200 205 Asn His Glu Glu Arg Asn Ser Leu Thr Leu Ser Glu AsnLys Ala Asn 210 215 220 Arg Ser Leu Gly Lys Leu Ala Lys Leu Phe Lys LeuPhe Ala Glu Asn 225 230 235 240 Gln Arg Leu Val Arg Glu Val Phe Arg ThrPhe Asp Leu Pro Ile Ala 245 250 255 Leu Leu Leu Leu Lys Met Phe Val ThrAsn Val Asn Leu Val Tyr His 260 265 270 Gly Val Gln Phe Gly Asn Asp ThrIle Glu Thr Ser Ser Tyr Thr Arg 275 280 285 Ile Val Gly Gln Trp Val ValIle Ser His Tyr Trp Ser Ala Val Leu 290 295 300 Leu Met Asn Val Val AspAsp Val Thr Arg Arg Ser Asp Leu Lys Met 305 310 315 320 Gly Asp Leu LeuArg Glu Phe Ser His Leu Glu Leu Val Lys Arg Asp 325 330 335 Phe His LeuGln Leu Glu Leu Phe Ser Asp His Leu Arg Cys His Pro 340 345 350 Ser ThrTyr Lys Val Cys Gly Leu Phe Ile Phe Asn Lys Gln Thr Ser 355 360 365 LeuAla Tyr Phe Phe Tyr Val Leu Val Gln Val Leu Val Leu Val Gln 370 375 380Phe Asp Leu Lys Asn Lys Val Glu Lys Arg Asn 385 390 395 37 408 PRTDrosophila melanogaster 37 Met Leu His Pro Lys Leu Gly Arg Val Met AsnVal Val Tyr Tyr His 1 5 10 15 Ser Val Val Phe Ala Leu Met Ser Thr ThrLeu Arg Ile Arg Ser Cys 20 25 30 Arg Lys Cys Leu Arg Leu Glu Lys Val SerArg Thr Tyr Thr Ile Tyr 35 40 45 Ser Phe Phe Val Gly Ile Phe Leu Phe LeuAsn Leu Tyr Phe Met Val 50 55 60 Pro Arg Ile Met Glu Asp Gly Tyr Met LysTyr Asn Ile Val Leu Gln 65 70 75 80 Trp Asn Phe Phe Val Met Leu Phe LeuArg Ala Ile Ala Val Val Ser 85 90 95 Cys Tyr Gly Thr Leu Trp Leu Lys ArgHis Lys Ile Ile Gln Leu Tyr 100 105 110 Lys Tyr Ser Leu Ile Tyr Trp LysArg Phe Gly His Ile Thr Arg Ala 115 120 125 Ile Val Asp Lys Lys Glu LeuLeu Asp Leu Gln Glu Ser Leu Ala Arg 130 135 140 Ile Met Ile Arg Lys IleIle Leu Leu Tyr Ser Ala Phe Leu Cys Ser 145 150 155 160 Thr Val Leu GlnTyr Gln Leu Leu Ser Val Ile Asn Pro Gln Ile Phe 165 170 175 Leu Ala PheCys Ala Arg Leu Thr His Phe Leu His Phe Leu Cys Val 180 185 190 Lys MetGly Phe Phe Gly Val Leu Val Leu Leu Asn His Gln Phe Leu 195 200 205 ValIle His Leu Ala Ile Asn Ala Leu His Gly Arg Lys Ala Arg Lys 210 215 220Lys Trp Lys Ala Leu Arg Ser Val Ala Ala Met His Leu Lys Thr Leu 225 230235 240 Arg Leu Ala Arg Arg Ile Phe Asp Met Phe Asp Ile Ala Asn Ala Thr245 250 255 Val Phe Ile Asn Met Phe Met Thr Ala Ile Asn Ile Leu Tyr HisAla 260 265 270 Val Gln Tyr Ser Asn Ser Ser Ile Lys Ser Asn Gly Trp GlyIle Leu 275 280 285 Phe Gly Asn Gly Leu Ile Val Phe Asn Phe Trp Gly ThrMet Ala Leu 290 295 300 Met Glu Met Leu Asp Ser Val Val Thr Ser Cys AsnAsn Thr Gly Gln 305 310 315 320 Gln Leu Arg Gln Leu Ser Asp Leu Pro LysVal Gly Pro Lys Met Gln 325 330 335 Arg Glu Leu Asp Tyr Phe Thr Met GlnLeu Arg Gln Asn Arg Leu Val 340 345 350 Tyr Lys Ile Cys Gly Ile Val GluLeu Asp Lys Pro Ala Cys Leu Ser 355 360 365 Tyr Ile Gly Ser Ile Leu SerAsn Val Ile Ile Leu Met Gln Phe Asp 370 375 380 Leu Arg Arg Gln Arg GlnPro Ile Asn Asp Arg Gln Tyr Leu Ile His 385 390 395 400 Leu Met Lys AsnLys Thr Lys Val 405 38 412 PRT Drosophila melanogaster 38 Met Asn GlnTyr Phe Leu Leu His Thr Tyr Phe Gln Val Ser Arg Leu 1 5 10 15 Ile GlyLeu Cys Asn Leu His Tyr Asp Ser Ser Asn His Arg Phe Ile 20 25 30 Leu AsnHis Val Pro Thr Val Val Tyr Cys Val Ile Leu Asn Val Val 35 40 45 Tyr LeuLeu Val Leu Pro Phe Ala Leu Phe Val Leu Thr Gly Asn Ile 50 55 60 Tyr HisCys Pro Asp Ala Gly Met Phe Gly Val Val Tyr Asn Val Val 65 70 75 80 AlaLeu Thr Lys Leu Leu Thr Met Leu Phe Leu Met Ser Ser Val Trp 85 90 95 IleGln Arg Arg Arg Leu Tyr Lys Leu Gly Asn Asp Leu Met Lys Met 100 105 110Leu His Lys Phe Arg Phe Asn Leu Gly Asn Asp Cys Arg Asn Arg Cys 115 120125 Leu Cys Lys Gly Leu Leu Thr Ser Ser Arg Phe Val Leu Leu Thr Gln 130135 140 Gln Leu Leu Thr Arg Asp Ser Val Val Asn Cys Glu Ser Asn Ser Ser145 150 155 160 Leu Arg Gln Ala Met Val Pro Tyr Gln Ser Ala Ala Ile ValTyr Ala 165 170 175 Leu Ile Met Ile Leu Leu Met Ser Tyr Val Asp Met ThrVal Tyr Met 180 185 190 Val Glu Val Ala Gly Asn Trp Leu Leu Val Asn MetThr Gln Gly Val 195 200 205 Arg Glu Met Val Gln Asp Leu Glu Val Leu ProGlu Arg Asn Gly Ile 210 215 220 Pro Arg Glu Met Gly Leu Met Gln Ile LeuAla Ala Trp Arg Lys Leu 225 230 235 240 Trp Arg Arg Cys Arg Arg Leu AspAla Leu Leu Lys Gln Phe Val Asp 245 250 255 Ile Phe Gln Trp Gln Val LeuPhe Asn Leu Leu Thr Thr Tyr Ile Phe 260 265 270 Ser Ile Ala Val Leu PheArg Leu Trp Ile Tyr Leu Glu Phe Asp Lys 275 280 285 Asn Phe His Leu TrpLys Gly Ile Leu Tyr Ala Ile Ile Phe Leu Thr 290 295 300 His His Val GluIle Val Met Gln Phe Ser Ile Phe Glu Ile Asn Arg 305 310 315 320 Cys LysTrp Leu Gly Leu Leu Glu Asp Val Gly Asn Leu Trp Asp Ile 325 330 335 AsnTyr Ser Gly Arg Gln Cys Ile Lys Ser Ser Gly Thr Ile Leu Ser 340 345 350Arg Lys Leu Glu Phe Ser Leu Leu Tyr Met Asn Arg Lys Leu Gln Leu 355 360365 Asn Pro Lys Arg Val Arg Arg Leu His Ile Val Gly Leu Phe Asp Ile 370375 380 Ser Asn Leu Thr Val His Asn Met Thr Arg Ser Ile Ile Thr Asn Val385 390 395 400 Leu Val Leu Cys Gln Ile Ala Tyr Lys Lys Tyr Gly 405 41039 390 PRT Drosophila melanogaster 39 Met Ala Asp Leu Leu Lys Leu CysLeu Arg Ile Ala Tyr Ala Tyr Gly 1 5 10 15 Arg Leu Thr Gly Val Ile AsnPhe Lys Ile Asp Leu Lys Thr Gly Gln 20 25 30 Ala Leu Val Thr Arg Gly AlaThr Leu Ile Ser Val Ser Thr His Leu 35 40 45 Leu Ile Phe Ala Leu Leu LeuTyr Gln Thr Met Arg Lys Ser Val Val 50 55 60 Asn Val Met Trp Lys Tyr AlaAsn Ser Leu His Glu Tyr Val Phe Leu 65 70 75 80 Val Ile Ala Gly Phe ArgVal Val Cys Val Phe Leu Glu Leu Val Ser 85 90 95 Arg Trp Ser Gln Arg ArgThr Phe Val Arg Leu Phe Asn Ser Phe Arg 100 105 110 Arg Leu Tyr Gln ArgAsn Pro Asp Ile Ile Gln Tyr Cys Arg Arg Ser 115 120 125 Ile Val Ser LysPhe Phe Cys Val Thr Met Thr Glu Thr Leu His Ile 130 135 140 Ile Val ThrLeu Ala Met Met Arg Asn Arg Leu Ser Ile Ala Leu Ala 145 150 155 160 LeuArg Ile Trp Ala Val Leu Ser Leu Thr Ala Ile Ile Asn Val Ile 165 170 175Ile Thr Gln Tyr Tyr Val Ala Thr Ala Cys Val Arg Gly Arg Tyr Ala 180 185190 Leu Leu Asn Lys Asp Leu Gln Ala Ile Val Thr Glu Ser Gln Ser Leu 195200 205 Val Pro Asn Gly Gly Gly Val Phe Val Thr Lys Cys Cys Tyr Leu Ala210 215 220 Asp Arg Leu Glu Arg Ile Ala Lys Ser Gln Ser Asp Leu Gln GluLeu 225 230 235 240 Val Glu Asn Leu Ser Thr Ala Tyr Glu Gly Glu Val ValCys Leu Val 245 250 255 Ile Thr Tyr Tyr Leu Asn Met Leu Gly Thr Ser TyrLeu Leu Phe Ser 260 265 270 Ile Ser Lys Tyr Gly Asn Phe Gly Asn Asn LeuLeu Val Ile Ile Thr 275 280 285 Leu Cys Gly Ile Val Tyr Phe Val Phe TyrVal Val Asp Cys Trp Ile 290 295 300 Asn Ala Phe Asn Val Phe Tyr Leu LeuAsp Ala His Asp Lys Met Val 305 310 315 320 Lys Leu Leu Asn Lys Arg ThrLeu Phe Gln Pro Gly Leu Asp His Arg 325 330 335 Leu Glu Met Val Phe GluAsn Phe Ala Leu Asn Leu Val Arg Asn Pro 340 345 350 Leu Lys Leu His MetTyr Gly Leu Phe Glu Phe Gly Arg Gly Thr Ser 355 360 365 Phe Ala Val PheAsn Ser Leu Leu Thr His Ser Leu Leu Leu Ile Gln 370 375 380 Tyr Asp ValGln Asn Phe 385 390 40 394 PRT Drosophila melanogaster 40 Met Val AspLeu Val Lys Thr Ile Leu Leu Ile Ala Tyr Trp Tyr Gly 1 5 10 15 Leu AlaVal Gly Val Ser Asn Phe Glu Val Asp Trp Leu Thr Gly Glu 20 25 30 Ala IleAla Thr Arg Arg Thr Thr Ile Tyr Ala Ala Val His Asn Ala 35 40 45 Ser LeuIle Thr Leu Leu Ile Leu Phe Asn Leu Gly Asn Asn Ser Leu 50 55 60 Lys SerGlu Phe Ile Ser Ala Arg Tyr Leu His Glu Tyr Phe Phe Met 65 70 75 80 LeuMet Thr Ala Val Arg Ile Ser Ala Val Leu Leu Ser Leu Ile Thr 85 90 95 ArgTrp Tyr Gln Arg Ser Arg Phe Ile Arg Ile Trp Asn Gln Ile Leu 100 105 110Ala Leu Val Arg Asp Arg Pro Gln Val Val Arg Gly Arg Trp Tyr Arg 115 120125 Arg Ser Ile Ile Leu Lys Phe Val Phe Cys Val Leu Ser Asp Ser Leu 130135 140 His Thr Ile Ser Asp Val Ser Ala Gln Arg Lys Arg Ile Thr Ala Asp145 150 155 160 Leu Ile Val Lys Leu Ser Leu Leu Ala Thr Leu Thr Thr IlePhe Asn 165 170 175 Met Ile Val Cys Gln Tyr Tyr Leu Ala Met Val Gln ValIle Gly Leu 180 185 190 Tyr Lys Ile Leu Leu Gln Asp Leu Arg Cys Leu ValArg Gln Ala Glu 195 200 205 Cys Ile Cys Ser Ile Arg Asn Arg Arg Gly GlyVal Tyr Ser Ile Gln 210 215 220 Cys Cys Ser Leu Ala Asp Gln Leu Asp LeuIle Ala Glu Arg His Tyr 225 230 235 240 Phe Leu Lys Asp Arg Leu Asp GluMet Ser Asp Leu Phe Gln Ile Gln 245 250 255 Ser Leu Ser Met Ser Leu ValTyr Phe Phe Ser Thr Met Gly Ser Ile 260 265 270 Tyr Phe Ser Val Cys SerIle Leu Tyr Ser Ser Thr Gly Phe Gly Ser 275 280 285 Thr Tyr Trp Gly LeuLeu Leu Ile Val Leu Ser Thr Ala Ser Phe Tyr 290 295 300 Met Asp Asn TrpLeu Ser Val Asn Ile Gly Phe His Ile Arg Asp Gln 305 310 315 320 Gln AspGlu Leu Phe Arg Val Leu Ala Asp Arg Thr Leu Phe Tyr Arg 325 330 335 GluLeu Asp Asn Arg Leu Glu Ala Ala Phe Glu Asn Phe Gln Leu Gln 340 345 350Leu Ala Ser Asn Arg His Glu Phe Tyr Val Met Gly Leu Phe Lys Met 355 360365 Glu Arg Gly Arg Leu Ile Ala Met Leu Ser Ser Val Ile Thr His Thr 370375 380 Met Val Leu Val Gln Trp Glu Ile Gln Asn 385 390 41 405 PRTDrosophila melanogaster 41 Met Arg Ser Ser Ala Thr Lys Gly Ala Lys LeuLys Asn Ser Pro Arg 1 5 10 15 Glu Arg Leu Ser Ser Phe Asn Pro Gln TyrAla Glu Arg Tyr Lys Glu 20 25 30 Leu Tyr Arg Thr Leu Phe Trp Leu Leu LeuIle Ser Val Leu Ala Asn 35 40 45 Thr Ala Pro Ile Thr Ile Leu Pro Gly CysPro Asn Arg Phe Tyr Arg 50 55 60 Leu Val His Leu Ser Trp Met Ile Leu TrpTyr Gly Leu Phe Val Leu 65 70 75 80 Gly Ser Tyr Trp Glu Phe Val Leu ValThr Thr Gln Arg Val Ser Leu 85 90 95 Asp Arg Tyr Leu Asn Ala Ile Glu SerAla Ile Tyr Val Val His Ile 100 105 110 Phe Ser Ile Met Leu Leu Thr TrpGln Cys Arg Asn Trp Ala Pro Lys 115 120 125 Leu Met Thr Asn Ile Val ThrSer Asp Leu Asn Arg Ala Tyr Thr Ile 130 135 140 Asp Cys Asn Arg Thr LysArg Phe Ile Arg Leu Gln Leu Phe Leu Val 145 150 155 160 Gly Ile Phe AlaCys Leu Ala Ile Phe Phe Asn Ile Trp Thr His Lys 165 170 175 Phe Val ValTyr Arg Ser Ile Leu Ser Ile Asn Ser Tyr Val Met Pro 180 185 190 Asn IleIle Ser Ser Ile Ser Phe Ala Gln Tyr Tyr Leu Leu Leu Gln 195 200 205 GlyIle Ala Trp Arg Gln Arg Arg Leu Thr Glu Gly Leu Glu Arg Glu 210 215 220Leu Thr His Leu His Ser Pro Arg Ile Ser Glu Val Gln Lys Ile Arg 225 230235 240 Met His His Ala Asn Leu Ile Asp Phe Thr Lys Ala Val Asn Arg Thr245 250 255 Phe Gln Tyr Ser Ile Leu Leu Leu Phe Val Gly Cys Phe Leu AsnPhe 260 265 270 Asn Leu Val Leu Phe Leu Val Tyr Gln Gly Ile Glu Asn ProSer Met 275 280 285 Ala Asp Phe Thr Lys Trp Val Cys Met Leu Leu Trp LeuAla Met His 290 295 300 Val Gly Lys Val Cys Ser Ile Leu His Phe Asn GlnSer Ile Gln Asn 305 310 315 320 Glu His Ser Thr Cys Leu Thr Leu Leu SerArg Val Ser Tyr Ala Arg 325 330 335 Lys Asp Ile Gln Asp Thr Ile Thr HisPhe Ile Ile Gln Met Arg Thr 340 345 350 Asn Val Arg Gln His Val Val CysGly Val Ile Asn Leu Asp Leu Lys 355 360 365 Phe Leu Thr Thr Leu Leu ValAla Ser Ala Asp Phe Phe Ile Phe Leu 370 375 380 Leu Gln Tyr Asp Val ThrTyr Glu Ala Leu Ser Lys Ser Val Gln Gly 385 390 395 400 Asn Val Thr ArgTyr 405 42 399 PRT Drosophila melanogaster 42 Met Asp Ser Ser Tyr TrpGlu Asn Leu Leu Leu Thr Ile Asn Arg Phe 1 5 10 15 Leu Gly Val Tyr ProSer Gly Arg Val Gly Val Leu Arg Trp Leu His 20 25 30 Thr Leu Trp Ser LeuPhe Leu Leu Met Tyr Ile Trp Thr Gly Ser Ile 35 40 45 Val Lys Cys Leu GluPhe Thr Val Glu Ile Pro Thr Ile Glu Lys Leu 50 55 60 Leu Tyr Leu Met GluPhe Pro Gly Asn Met Ala Thr Ile Ala Ile Leu 65 70 75 80 Val Tyr Tyr AlaVal Leu Asn Arg Pro Leu Ala His Gly Ala Glu Leu 85 90 95 Gln Ile Glu ArgIle Ile Thr Gly Leu Lys Gly Lys Ala Lys Arg Leu 100 105 110 Val Tyr LysArg His Gly Gln Arg Thr Leu His Leu Met Ala Thr Thr 115 120 125 Leu ValPhe His Gly Leu Cys Val Leu Val Asp Val Val Asn Tyr Asp 130 135 140 PheGlu Phe Trp Thr Thr Trp Ser Ser Asn Ser Val Tyr Asn Leu Pro 145 150 155160 Gly Leu Met Met Ser Leu Gly Val Leu Gln Tyr Ala Gln Pro Val His 165170 175 Phe Leu Trp Leu Val Met Asp Gln Met Arg Met Cys Leu Lys Glu Leu180 185 190 Lys Leu Leu Gln Arg Pro Pro Gln Gly Ser Thr Lys Leu Asp AlaCys 195 200 205 Tyr Glu Ser Ala Phe Ala Val Leu Val Asp Ala Gly Gly GlySer Ala 210 215 220 Leu Met Ile Glu Glu Met Arg Tyr Thr Cys Asn Leu IleGlu Gln Val 225 230 235 240 His Ser Gln Phe Leu Leu Arg Phe Gly Leu TyrLeu Val Leu Asn Leu 245 250 255 Leu Asn Ser Leu Val Ser Ile Cys Val GluLeu Tyr Leu Ile Phe Asn 260 265 270 Phe Phe Glu Thr Pro Leu Trp Glu GluSer Val Leu Leu Val Tyr Arg 275 280 285 Leu Leu Trp Leu Ala Met His GlyGly Arg Ile Trp Phe Ile Leu Ser 290 295 300 Val Asn Glu Gln Ile Leu GluGln Lys Cys Asn Leu Cys Gln Leu Leu 305 310 315 320 Asn Glu Leu Glu ValCys Ser Ser Arg Leu Gln Arg Thr Ile Asn Arg 325 330 335 Phe Leu Leu GlnLeu Gln Arg Ser Ile Asp Gln Pro Leu Glu Ala Cys 340 345 350 Gly Ile ValThr Leu Asp Thr Arg Ser Leu Gly Gly Phe Ile Gly Val 355 360 365 Leu MetAla Ile Val Ile Phe Leu Ile Gln Ile Gly Leu Gly Asn Lys 370 375 380 SerLeu Met Gly Val Ala Leu Asn Arg Ser Asn Trp Val Tyr Val 385 390 395 43392 PRT Drosophila melanogaster 43 Met Lys Ile Tyr Gln Asp Ile Tyr ProIle Ser Lys Pro Ser Gln Ile 1 5 10 15 Phe Ala Ile Leu Pro Phe Tyr SerGly Asp Val Asp Asp Gly Phe Arg 20 25 30 Phe Gly Gly Leu Gly Arg Trp TyrGly Arg Leu Val Ala Leu Ile Ile 35 40 45 Leu Ile Gly Ser Leu Thr Leu GlyGlu Asp Val Leu Phe Ala Ser Lys 50 55 60 Glu Tyr Arg Leu Val Ala Ser AlaGln Gly Asp Thr Glu Glu Ile Asn 65 70 75 80 Arg Thr Ile Glu Thr Leu LeuCys Ile Ile Ser Tyr Thr Met Val Val 85 90 95 Leu Ser Ser Val Gln Asn AlaSer Arg His Phe Arg Thr Leu His Asp 100 105 110 Ile Ala Lys Ile Asp GluTyr Leu Leu Ala Asn Gly Phe Arg Glu Thr 115 120 125 Tyr Ser Cys Arg AsnLeu Thr Ile Leu Val Thr Ser Ala Ala Gly Gly 130 135 140 Val Leu Ala ValAla Phe Tyr Tyr Ile His Tyr Arg Ser Gly Ile Gly 145 150 155 160 Ala LysArg Gln Ile Ile Leu Leu Leu Ile Tyr Phe Leu Gln Leu Leu 165 170 175 TyrSer Thr Leu Leu Ala Leu Tyr Leu Arg Thr Leu Met Met Asn Leu 180 185 190Ala Gln Arg Ile Gly Phe Leu Asn Gln Lys Leu Asp Thr Phe Asn Leu 195 200205 Gln Asp Cys Gly His Met Glu Asn Trp Arg Glu Leu Ser Asn Leu Ile 210215 220 Glu Val Leu Cys Lys Phe Arg Tyr Ile Thr Glu Asn Ile Asn Cys Val225 230 235 240 Ala Gly Val Ser Leu Leu Phe Tyr Phe Gly Phe Ser Phe TyrThr Val 245 250 255 Thr Asn Gln Ser Tyr Leu Ala Phe Ala Thr Leu Thr AlaGly Ser Leu 260 265 270 Ser Ser Lys Thr Glu Val Ala Asp Thr Ile Gly LeuSer Cys Ile Trp 275 280 285 Val Leu Ala Glu Thr Ile Thr Met Ile Val IleCys Ser Ala Cys Asp 290 295 300 Gly Leu Ala Ser Glu Val Asn Gly Thr AlaGln Ile Leu Ala Arg Ile 305 310 315 320 Tyr Gly Lys Ser Lys Gln Phe GlnAsn Leu Ile Asp Lys Phe Leu Thr 325 330 335 Lys Ser Ile Lys Gln Asp LeuGln Phe Thr Ala Tyr Gly Phe Phe Ser 340 345 350 Ile Asp Asn Ser Thr LeuPhe Lys Ile Phe Ser Ala Val Thr Thr Tyr 355 360 365 Leu Val Ile Leu IleGln Phe Lys Gln Leu Glu Asp Ser Lys Asn Leu 370 375 380 Ser Arg Ser TyrGln Leu Val Met 385 390 44 424 PRT Drosophila melanogaster 44 Met ProArg Trp Leu Gln Leu Pro Gly Met Ser Ala Leu Gly Ile Leu 1 5 10 15 TyrSer Leu Thr Arg Val Phe Gly Leu Met Ala Thr Ala Asn Trp Ser 20 25 30 ProArg Gly Ile Lys Arg Val Arg Gln Ser Leu Tyr Leu Arg Ile His 35 40 45 GlyCys Val Met Leu Ile Phe Val Gly Cys Phe Ser Pro Phe Ala Phe 50 55 60 TrpCys Ile Phe Gln Arg Met Ala Phe Leu Arg Gln Asn Arg Ile Leu 65 70 75 80Leu Met Ile Gly Phe Asn Arg Tyr Val Leu Leu Leu Val Cys Ala Phe 85 90 95Met Thr Leu Trp Ile His Cys Phe Lys Gln Ala Glu Ile Ile Gly Cys 100 105110 Leu Asn Arg Leu Leu Lys Cys Arg Arg Arg Leu Arg Arg Leu Met His 115120 125 Thr Arg Lys Leu Lys Asp Ser Met Asp Cys Leu Ala Thr Lys Gly His130 135 140 Leu Leu Glu Val Val Val Leu Leu Ser Ser Tyr Leu Leu Ser MetAla 145 150 155 160 Gln Pro Ile Gln Ile Leu Lys Asp Asp Pro Glu Val ArgArg Asn Phe 165 170 175 Met Tyr Ala Cys Ser Leu Val Phe Val Ser Val CysGln Ala Ile Leu 180 185 190 Gln Leu Ser Leu Gly Met Tyr Thr Met Ala IleLeu Phe Leu Gly His 195 200 205 Leu Val Arg His Ser Asn Leu Leu Leu AlaLys Ile Leu Ala Asp Ala 210 215 220 Glu His Ile Phe Glu Ser Ser Gln LysAla Gly Phe Trp Pro Asn Arg 225 230 235 240 Gln Glu Leu Tyr Lys Gly GlnGln Lys Trp Leu Ala Leu Glu Leu Trp 245 250 255 Arg Leu Leu His Val HisHis Gln Leu Leu Lys Leu His Arg Ser Ile 260 265 270 Cys Ser Leu Cys AlaVal Gln Ala Val Cys Phe Leu Gly Phe Val Pro 275 280 285 Leu Glu Cys ThrIle His Leu Phe Phe Thr Tyr Phe Met Lys Tyr Ser 290 295 300 Lys Phe IleLeu Arg Lys Tyr Gly Arg Ser Phe Pro Leu Asn Tyr Phe 305 310 315 320 AlaIle Ala Phe Leu Val Gly Leu Phe Thr Asn Leu Leu Leu Val Ile 325 330 335Leu Pro Thr Tyr Tyr Ser Glu Arg Arg Phe Asn Cys Thr Arg Glu Ile 340 345350 Ile Lys Gly Gly Gly Leu Ala Phe Pro Ser Arg Ile Thr Val Lys Gln 355360 365 Leu Arg His Thr Met His Phe Tyr Gly Leu Tyr Leu Lys Asn Val Glu370 375 380 His Val Phe Ala Val Ser Ala Cys Gly Leu Phe Lys Leu Asn AsnAla 385 390 395 400 Ile Leu Phe Cys Ile Val Gly Ala Ile Leu Glu Tyr LeuMet Ile Leu 405 410 415 Ile Gln Phe Asp Lys Val Leu Asn 420 45 92 PRTDrosophila melanogaster 45 Cys Gln Leu Leu Asn Gly Tyr Arg Thr Glu HisAla Gly Gly Asn Tyr 1 5 10 15 Leu Leu Ala Ser Asp Phe Asp Arg Arg LeuLys Val Phe Leu Gln Trp 20 25 30 Lys Thr Ser Asp Ser Ala Glu Ser Ala SerGly Arg Leu Gly Ser Gln 35 40 45 Tyr Thr Phe Val Gly His Lys Lys Lys GlnThr Gly Leu Thr Ile Lys 50 55 60 Leu Ala Glu Asn Gly Phe Cys Cys Trp ValLeu Leu Leu Arg Tyr Phe 65 70 75 80 Ser Val Leu Ile Lys Ile Val Lys TyrLys Ile Pro 85 90 46 416 PRT Drosophila melanogaster 46 Met Ala Val LeuTyr Phe Phe Arg Glu Pro Glu Thr Val Phe Asp Cys 1 5 10 15 Ala Ala PheIle Cys Ile Leu Gln Phe Leu Met Gly Cys Asn Gly Phe 20 25 30 Gly Ile ArgArg Ser Thr Phe Arg Ile Ser Trp Ala Ser Arg Ile Tyr 35 40 45 Ser Met SerVal Ala Ile Ala Ala Phe Cys Cys Leu Phe Gly Ser Leu 50 55 60 Ser Val LeuLeu Ala Glu Glu Asp Ile Arg Glu Arg Leu Ala Lys Ala 65 70 75 80 Asp AsnLeu Val Leu Ser Ile Ser Ala Leu Glu Leu Leu Met Ser Thr 85 90 95 Leu ValPhe Gly Val Thr Val Ile Ser Leu Gln Val Phe Ala Arg Arg 100 105 110 HisLeu Gly Ile Tyr Gln Arg Leu Ala Ala Leu Asp Ala Arg Leu Met 115 120 125Ser Asp Phe Gly Ala Asn Leu Asn Tyr Arg Lys Met Leu Arg Lys Asn 130 135140 Ile Ala Val Leu Gly Ile Val Thr Thr Ile Tyr Leu Met Ala Ile Asn 145150 155 160 Ser Ala Ala Val Gln Val Ala Ser Gly His Arg Ala Leu Phe LeuLeu 165 170 175 Phe Ala Leu Cys Tyr Thr Ile Val Thr Gly Gly Pro His PheThr Gly 180 185 190 Tyr Val His Met Thr Leu Ala Glu Met Leu Gly Ile ArgPhe Arg Leu 195 200 205 Leu Gln Gln Leu Leu Gln Pro Glu Phe Leu Asn TrpArg Phe Pro Gln 210 215 220 Leu His Val Gln Glu Leu Arg Ile Arg Gln ValVal Ser Met Ile Gln 225 230 235 240 Glu Leu His Tyr Leu Ile Gln Glu IleAsn Arg Val Tyr Ala Leu Ser 245 250 255 Leu Trp Ala Ala Met Ala His AspLeu Ala Met Ser Thr Ser Glu Leu 260 265 270 Tyr Ile Leu Phe Gly Gln SerVal Gly Ile Gly Gln Gln Asn Glu Glu 275 280 285 Glu Asn Gly Ser Cys TyrArg Met Leu Gly Tyr Leu Ala Leu Val Met 290 295 300 Ile Pro Pro Leu TyrLys Leu Leu Ile Ala Pro Phe Tyr Cys Asp Arg 305 310 315 320 Thr Ile TyrGlu Ala Arg Arg Cys Leu Arg Leu Val Glu Lys Leu Asp 325 330 335 Asp TrpPhe Pro Gln Lys Ser Ser Leu Arg Pro Leu Val Glu Ser Leu 340 345 350 MetSer Trp Arg Ile Gln Ala Lys Ile Gln Phe Thr Ser Gly Leu Asp 355 360 365Val Val Leu Ser Arg Lys Val Ile Gly Leu Phe Thr Ser Ile Leu Val 370 375380 Asn Tyr Leu Leu Ile Leu Ile Gln Phe Ala Met Thr Gln Lys Met Gly 385390 395 400 Glu Gln Ile Glu Gln Gln Lys Ile Ala Leu Gln Glu Trp Ile GlyPhe 405 410 415 47 339 PRT Drosophila melanogaster 47 Met Arg Val HisGln Arg Gln Ser Ala Val Ile Ile Gln Met Gly His 1 5 10 15 Pro Pro PheMet Ser Leu Lys Gly Gly Lys Ser Gly Phe Gly Ser Ile 20 25 30 Val Trp ProSer Ala Met Arg Glu Val Asn Leu Leu Asn Arg Phe Thr 35 40 45 Arg Gln PheLeu Phe Leu Ile Val Leu Val Thr Gln Ile Cys Gly Val 50 55 60 Ala Thr PheVal Tyr Asn Ser Lys Ala Gln Cys Phe Arg Gln Ser Gly 65 70 75 80 Phe LeuArg Phe Tyr Ser Ser Leu Val Leu Ile Phe Leu Ala Leu Phe 85 90 95 Leu IleVal Thr Thr Ser Lys Met Phe His Asn Leu Gln Ala Val Trp 100 105 110 ProTyr Val Val Gly Ser Val Ile Ile Leu Val Val Arg Ile His Gly 115 120 125Leu Leu Glu Ser Ala Glu Ile Val Glu Leu Leu Asn Gln Met Leu Arg 130 135140 Ile Met Arg Gln Val Asn Leu Met Ala Arg His Pro Asn Leu Phe Arg 145150 155 160 Leu Lys His Leu Leu Leu Leu Leu Leu Ala Leu Gln Asn Leu LeuArg 165 170 175 Ser Leu Asn Thr Ile Val Gly Ile Ser Asn His Ser Ala GluAla Tyr 180 185 190 Asp Ser Phe Leu Asn Ser Val Ile Leu Leu Ile Ile LeuAla Val Leu 195 200 205 Leu Ser Phe Leu Leu Gln Ile Thr Ile Asn Ile CysLeu Phe Val Val 210 215 220 Leu Ile Ala Thr Tyr Ser Glu Leu His His CysThr Arg Arg Ile Ser 225 230 235 240 Asn Asp Met Asp Lys Leu Arg Leu HisSer Val His Glu Ser Gly Gln 245 250 255 Phe Met Val Leu Val Lys Gln LeuGln Gly Ile Thr Glu Lys Leu Ile 260 265 270 Arg Leu Arg Gln Asn Val PheHis Ile Thr Val Arg Ile Ile Arg His 275 280 285 Phe Arg Phe His Trp LeuCys Ala Ile Ile Tyr Gly Leu Leu Pro Phe 290 295 300 Phe Ser Leu Thr AlaLys Asp Gln Asn Gly Phe Asn Phe Leu Ile Ile 305 310 315 320 Ser Ala LeuAsn Ile Ile Phe Gln Trp Thr Ile Phe Ala Ile Leu Ser 325 330 335 Arg GluSer 48 417 PRT Drosophila melanogaster 48 Met Thr Gly Lys Arg Ala GluSer Trp Ser Arg Leu Leu Leu Leu Trp 1 5 10 15 Leu Tyr Arg Cys Ala ArgGly Leu Leu Val Leu Ser Ser Ser Leu Asp 20 25 30 Arg Asp Lys Leu Gln LeuLys Ala Thr Lys Gln Gly Ser Arg Asn Arg 35 40 45 Phe Leu His Ile Leu TrpArg Cys Ile Val Val Met Ile Tyr Ala Gly 50 55 60 Leu Trp Pro Met Leu ThrSer Ala Val Ile Gly Lys Arg Leu Glu Ser 65 70 75 80 Tyr Ala Asp Val LeuAla Leu Ala Gln Ser Met Ser Val Ser Ile Leu 85 90 95 Ala Val Ile Ser PheVal Ile Gln Ala Arg Gly Glu Asn Gln Phe Arg 100 105 110 Glu Val Leu AsnArg Tyr Leu Ala Leu Tyr Gln Arg Ile Cys Leu Thr 115 120 125 Thr Arg LeuArg His Leu Phe Pro Thr Lys Phe Val Val Phe Phe Leu 130 135 140 Leu LysLeu Phe Phe Thr Leu Cys Gly Cys Phe His Glu Ile Ile Pro 145 150 155 160Leu Phe Glu Asn Ser His Phe Asp Asp Ile Ser Gln Met Val Gly Thr 165 170175 Gly Phe Gly Ile Tyr Met Trp Leu Gly Thr Leu Cys Val Leu Asp Ala 180185 190 Cys Phe Leu Gly Phe Leu Val Ser Gly Ile Leu Tyr Glu His Met Ala195 200 205 Asn Asn Ile Ile Ala Met Leu Lys Arg Met Glu Pro Ile Glu SerGln 210 215 220 Asp Glu Arg Tyr Arg Met Thr Lys Tyr Arg Arg Met Gln LeuLeu Cys 225 230 235 240 Asp Phe Ala Asp Glu Leu Asp Glu Cys Ala Ala IleTyr Ser Glu Leu 245 250 255 Tyr His Val Thr Asn Ser Phe Arg Arg Ile LeuGln Trp Gln Ile Leu 260 265 270 Phe Tyr Ile Tyr Leu Asn Phe Ile Asn IleCys Leu Met Leu Tyr Gln 275 280 285 Tyr Ile Leu His Phe Leu Asn Asp AspGlu Val Val Phe Val Ser Ile 290 295 300 Val Met Ala Phe Val Lys Leu AlaAsn Leu Val Leu Leu Met Met Cys 305 310 315 320 Ala Asp Tyr Thr Val ArgGln Ser Glu Val Pro Lys Lys Leu Pro Leu 325 330 335 Asp Ile Val Cys SerAsp Met Asp Glu Arg Trp Asp Lys Ser Val Ser 340 345 350 Leu Leu Leu PheGlu Thr Phe Leu Gly Gln Leu Gln Thr Gln Arg Leu 355 360 365 Glu Ile LysVal Leu Gly Phe Phe His Leu Asn Asn Glu Phe Ile Leu 370 375 380 Leu IleLeu Ser Ala Ile Ile Ser Tyr Leu Phe Ile Leu Ile Gln Phe 385 390 395 400Gly Ile Thr Gly Gly Phe Glu Ala Ser Glu Asp Ile Lys Asn Phe Ala 405 410415 Asp 49 299 PRT Drosophila melanogaster 49 Met Gln Phe Trp Phe GlyGlu Glu Leu Ile Asn Leu Val Asn Arg Phe 1 5 10 15 Leu Gln Leu Phe ArgArg Met Gln Ser Leu Thr Asn Ser Pro Lys Asn 20 25 30 Arg Phe Gly Asp ArgAla Glu Phe Leu Leu Met Phe Ser Lys Val Phe 35 40 45 Ser Leu Leu Phe ValPhe Met Ala Phe Arg Leu Met Leu Ser Pro Trp 50 55 60 Phe Leu Leu Thr LeuVal Cys Asp Leu Tyr Thr Ser Val Gly Thr Gly 65 70 75 80 Met Ile Thr HisLeu Cys Phe Val Gly Tyr Leu Ser Ile Gly Val Leu 85 90 95 Tyr Arg Asp LeuAsn Asn Tyr Val Asp Cys Gln Leu Arg Ala Gln Leu 100 105 110 Arg Ser LeuAsn Gly Glu Asn Asn Ser Phe Arg Asn Asn Pro Gln Pro 115 120 125 Thr ArgGln Ala Ile Ser Asn Leu Asp Lys Cys Leu Tyr Leu Tyr Asp 130 135 140 GluIle His Gln Val Ser Arg Ser Phe Gln Gln Leu Phe Asp Leu Pro 145 150 155160 Leu Phe Leu Ser Leu Ala Gln Ser Leu Leu Ala Met Ser Met Val Ser 165170 175 Tyr His Ala Ile Leu Arg Arg Gln Tyr Ser Phe Asn Leu Trp Gly Leu180 185 190 Val Ile Lys Leu Leu Ile Asp Val Val Leu Leu Thr Met Ser ValHis 195 200 205 Ser Ala Val Asn Gly Ser Arg Leu Ile Arg Arg Leu Ser PheGlu Asn 210 215 220 Phe Tyr Val Thr Asp Ser Gln Ser Tyr His Gln Lys ValSer Pro Gly 225 230 235 240 Ala Ile Ile Leu Arg Ile Lys Tyr Asn Thr PhePro Ile Leu Gln Leu 245 250 255 Glu Leu Phe Leu Gly Arg Leu Gln His GlnGlu Leu Arg Val Phe Pro 260 265 270 Leu Gly Leu Phe Glu Val Ser Asn GluLeu Thr Leu Phe Phe Leu Ser 275 280 285 Ala Met Val Thr Tyr Leu Val PheLeu Val Gln 290 295 50 407 PRT Drosophila melanogaster 50 Met Ile GluArg Leu Lys Lys Val Ser Leu Pro Ala Leu Ser Ala Phe 1 5 10 15 Ile LeuPhe Cys Ser Cys His Tyr Gly Arg Ile Leu Gly Val Ile Cys 20 25 30 Phe AspIle Gly Gln Arg Thr Ser Asp Asp Ser Leu Val Val Arg Asn 35 40 45 Arg HisGln Phe Lys Trp Phe Cys Leu Ser Cys Arg Leu Ile Ser Val 50 55 60 Thr AlaVal Cys Cys Phe Cys Ala Pro Tyr Val Ala Asp Ile Glu Asp 65 70 75 80 ProTyr Glu Arg Leu Leu Gln Cys Phe Arg Leu Ser Ala Ser Leu Ile 85 90 95 CysGly Ile Cys Ile Ile Val Val Gln Val Cys Tyr Glu Lys Glu Leu 100 105 110Leu Arg Met Ile Ile Ser Phe Leu Arg Leu Phe Arg Arg Val Arg Arg 115 120125 Leu Ser Ser Leu Lys Arg Ile Gly Phe Gly Gly Lys Arg Glu Phe Phe 130135 140 Leu Leu Leu Phe Lys Phe Ile Cys Leu Val Tyr Glu Leu Tyr Ser Glu145 150 155 160 Ile Cys Gln Leu Trp His Leu Pro Asp Ser Leu Ser Leu PheAla Thr 165 170 175 Leu Cys Glu Ile Phe Leu Glu Ile Gly Ser Leu Met IleIle His Ile 180 185 190 Gly Phe Val Gly Tyr Leu Ser Val Ala Ala Leu TyrSer Glu Val Asn 195 200 205 Ser Phe Ala Arg Ile Glu Leu Arg Arg Gln LeuArg Ser Leu Glu Arg 210 215 220 Pro Val Gly Gly Pro Val Gly Arg Lys GlnLeu Arg Ile Val Glu Tyr 225 230 235 240 Arg Val Asp Glu Cys Ile Ser ValTyr Asp Glu Ile Glu Arg Val Gly 245 250 255 Arg Thr Phe His Arg Leu LeuGlu Leu Pro Val Leu Ile Ile Leu Leu 260 265 270 Gly Lys Ile Phe Ala ThrThr Ile Leu Ser Tyr Glu Val Ile Ile Arg 275 280 285 Pro Glu Leu Tyr AlaArg Lys Ile Gly Met Trp Gly Leu Val Val Lys 290 295 300 Ser Phe Ala AspVal Ile Leu Leu Thr Leu Ala Val His Glu Ala Val 305 310 315 320 Ser SerSer Arg Met Met Arg Arg Leu Ser Leu Glu Asn Phe Pro Ile 325 330 335 ThrAsp His Lys Ala Trp His Met Lys Val Ser Asp Leu Met Val Phe 340 345 350Leu Ile Lys Cys Ile Phe Phe Ser Arg Leu Gln Trp Glu Met Phe Leu 355 360365 Ser Arg Leu Asn Phe Phe Glu Phe Arg Val Arg Pro Leu Gly Leu Phe 370375 380 Glu Val Ser Asn Glu Val Ile Leu Leu Phe Leu Ser Ser Met Ile Thr385 390 395 400 Tyr Phe Thr Tyr Val Val Gln 405 51 363 PRT Drosophilamelanogaster 51 Met Ser Phe Tyr Ala Arg Phe Leu Ser Leu Val Cys Phe ArgLeu Arg 1 5 10 15 Lys Gln Lys Asp Asn Asn Val Trp Leu Glu Glu Ile TrpSer Asn Arg 20 25 30 Ser Arg Trp Lys Trp Ile Ser Val Thr Leu Arg Ile ValPro Leu Cys 35 40 45 Ile Tyr Ala Phe Thr Tyr Ala Glu Trp Ile Ser Asn ArgMet Leu Ile 50 55 60 Thr Glu Lys Phe Leu His Ser Cys Ser Leu Val Val SerIle Pro Cys 65 70 75 80 Tyr Leu Ser Ile Ile His Leu Lys Ile Cys His GlyPro Glu Val Thr 85 90 95 Lys Leu Val Asn Gln Tyr Leu His Ile Phe Arg LeuGly Thr Leu Asp 100 105 110 Ile Arg Arg Arg Ser Gln Phe Gly Gly Gly ArgGlu Leu Phe Leu Leu 115 120 125 Ile Leu Ser Val Cys Cys Gln Ile His GluTyr Val Phe Ile Leu Val 130 135 140 Ile Ala Ser Arg Leu Cys Gly Phe GlnHis Ile Ile Trp Trp Val Ser 145 150 155 160 Tyr Thr Tyr Val Phe Ile IleCys Asn Ser Ile Met Cys Phe Gly Phe 165 170 175 Ile Trp His Leu Ser LeuGly Val Leu Tyr Ala Glu Leu Asn Asp Asn 180 185 190 Leu Arg Phe Glu SerGly Phe Gln Thr Ala Phe Leu Arg Lys Gln Gln 195 200 205 Arg Ile Arg ValGln Lys Ser Met Ala Leu Phe Lys Glu Ile Ser Ser 210 215 220 Val Val ThrSer Leu Gln Asp Ile Phe Asn Val His Leu Phe Leu Ser 225 230 235 240 AlaLeu Leu Thr Leu Leu Gln Val Leu Val Val Trp Tyr Lys Met Ile 245 250 255Ile Asp Leu Gly Phe Ser Asp Phe Arg Ile Trp Ser Phe Ser Leu Lys 260 265270 Asn Leu Ile Gln Thr Leu Leu Pro Val Leu Ala Ile Gln Glu Ala Ala 275280 285 Asn Gln Phe Lys Gln Thr Arg Glu Arg Ala Leu Asp Ile Phe Leu Val290 295 300 Gly Lys Ser Lys His Trp Met Lys Ser Val Ser Lys Leu Ile AsnGln 305 310 315 320 Gly Ile Leu Gln Leu Ile Gly Leu Phe Asn Val Ser AsnGlu Leu Phe 325 330 335 Leu Ile Ile Val Ser Ala Met Phe Cys Tyr Leu ValPhe Val Thr Gln 340 345 350 Cys Val Ile Val Tyr Arg Arg Arg Tyr Val Ile355 360 52 404 PRT Drosophila melanogaster 52 Met Asp Phe Thr Ser AspTyr Ala His Arg Arg Met Val Lys Phe Leu 1 5 10 15 Thr Ile Ile Leu IleGly Phe Met Thr Val Phe Gly Leu Leu Ala Asn 20 25 30 Arg Tyr Arg Ala GlyArg Arg Glu Arg Phe Arg Phe Ser Lys Ala Asn 35 40 45 Leu Ala Phe Ala SerLeu Trp Ala Ile Ala Phe Ser Leu Val Tyr Gly 50 55 60 Arg Gln Ile Tyr LysGlu Tyr Gln Glu Gly Gln Ile Asn Leu Lys Asp 65 70 75 80 Ala Thr Thr LeuTyr Ser Tyr Met Asn Ile Thr Val Ala Val Ile Asn 85 90 95 Tyr Val Ser GlnMet Ile Ile Ser Asp His Val Ala Lys Val Leu Ser 100 105 110 Lys Val ProPhe Phe Asp Thr Leu Lys Glu Phe Arg Leu Asp Ser Arg 115 120 125 Ser LeuTyr Ile Ser Ile Val Leu Ala Leu Val Lys Thr Val Ala Phe 130 135 140 ProLeu Thr Ile Glu Val Ala Phe Ile Leu Gln Gln Arg Arg Gln His 145 150 155160 Pro Glu Met Ser Leu Ile Trp Thr Leu Tyr Arg Leu Phe Pro Leu Ile 165170 175 Ile Ser Asn Phe Leu Asn Asn Cys Tyr Phe Gly Ala Met Val Val Val180 185 190 Lys Glu Ile Leu Tyr Ala Leu Asn Arg Arg Leu Glu Ala Gln LeuGln 195 200 205 Glu Val Asn Leu Leu Gln Arg Lys Asp Gln Leu Lys Leu TyrThr Lys 210 215 220 Tyr Tyr Arg Met Gln Arg Phe Cys Ala Leu Ala Asp GluLeu Asp Gln 225 230 235 240 Leu Ala Tyr Arg Tyr Arg Leu Ile Tyr Val HisSer Gly Lys Tyr Leu 245 250 255 Thr Pro Met Ser Leu Ser Met Ile Leu SerLeu Ile Cys His Leu Leu 260 265 270 Gly Ile Thr Val Gly Phe Tyr Ser LeuTyr Tyr Ala Ile Ala Asp Thr 275 280 285 Leu Ile Met Gly Lys Pro Tyr AspGly Leu Gly Ser Leu Ile Asn Leu 290 295 300 Val Phe Leu Ser Ile Ser LeuAla Glu Ile Thr Leu Leu Thr His Leu 305 310 315 320 Cys Asn His Leu LeuVal Ala Thr Arg Arg Ser Ala Val Ile Leu Gln 325 330 335 Glu Met Asn LeuGln His Ala Asp Ser Arg Tyr Arg Gln Ala Val His 340 345 350 Gly Phe ThrLeu Leu Val Thr Val Thr Lys Tyr Gln Ile Lys Pro Leu 355 360 365 Gly LeuTyr Glu Leu Asp Met Arg Leu Ile Ser Asn Val Phe Ser Ala 370 375 380 ValAla Ser Phe Leu Leu Ile Leu Val Gln Ala Asp Leu Ser Gln Arg 385 390 395400 Phe Lys Met Gln 53 352 PRT Drosophila melanogaster 53 Met Arg PheLeu Arg Arg Gln Thr Arg Arg Leu Arg Ser Ile Trp Gln 1 5 10 15 Arg SerLeu Pro Val Arg Phe Arg Arg Gly Lys Leu His Thr Gln Leu 20 25 30 Val ThrIle Cys Leu Tyr Ala Thr Val Phe Leu Asn Ile Leu Tyr Gly 35 40 45 Val TyrLeu Gly Arg Phe Ser Phe Arg Arg Lys Lys Phe Val Phe Ser 50 55 60 Lys GlyLeu Thr Ile Tyr Ser Leu Phe Val Ala Thr Phe Phe Ala Leu 65 70 75 80 PheTyr Ile Trp Asn Ile Tyr Asn Glu Ile Ser Thr Gly Gln Ile Asn 85 90 95 LeuArg Asp Thr Ile Gly Ile Tyr Cys Tyr Met Asn Val Cys Val Cys 100 105 110Leu Phe Asn Tyr Val Thr Gln Trp Glu Lys Thr Leu Gln Ile Ile Arg 115 120125 Phe Gln Asn Ser Val Pro Leu Phe Lys Val Leu Asp Ser Leu Asp Ile 130135 140 Ser Ala Met Ile Val Trp Arg Ala Phe Ile Tyr Gly Leu Leu Lys Ile145 150 155 160 Val Phe Cys Pro Leu Ile Thr Tyr Ile Thr Leu Ile Leu TyrHis Arg 165 170 175 Arg Ser Ile Ser Glu Ser Gln Trp Thr Ser Val Thr ThrThr Lys Thr 180 185 190 Met Leu Pro Leu Ile Val Ser Asn Gln Ile Asn AsnCys Phe Phe Gly 195 200 205 Gly Leu Val Leu Ala Asn Leu Ile Phe Ala AlaVal Asn Arg Lys Leu 210 215 220 His Gly Ile Val Lys Glu Ala Asn Met LeuGln Ser Pro Val Gln Met 225 230 235 240 Asn Leu His Lys Pro Tyr Tyr ArgMet Arg Arg Phe Cys Glu Leu Ala 245 250 255 Asp Leu Leu Asp Glu Leu AlaArg Lys Tyr Gly Phe Thr Ala Ser Arg 260 265 270 Ser Lys Asn Tyr Leu ArgPhe Thr Asp Trp Ser Met Val Leu Ser Met 275 280 285 Leu Met Asn Leu LeuGly Ile Thr Met Gly Cys Tyr Asn Gln Tyr Leu 290 295 300 Ala Ile Ala AspHis Tyr Ile Asn Glu Glu Pro Phe Asp Leu Phe Leu 305 310 315 320 Ala IleVal Leu Val Val Phe Leu Ala Val Pro Phe Leu Glu Leu Val 325 330 335 MetVal Ala Arg Ile Ser Asn Gln Thr Leu Val Glu Val Ile Val Ile 340 345 35054 160 PRT Drosophila melanogaster 54 Ile Glu Arg Phe Val Cys Ala GlnLeu Val His Glu Ala Tyr Lys Gln 1 5 10 15 Phe Ala Ser Asn Gly Phe ArgPhe Leu Asp Ala Leu Gly Cys Tyr Glu 20 25 30 His Ser Ala Leu Gly Arg AlaArg Pro Leu Ser Arg Arg Gly Tyr Ala 35 40 45 Ile Lys Val Ser Asp His ProAla Thr Pro Pro His Tyr His Met Pro 50 55 60 Pro Pro Lys Gln Pro Pro SerHis Leu Ala Val Gln His Ala Thr Leu 65 70 75 80 Thr Ser Gly Leu Arg GlnLeu Ser Phe Ser Cys Val Asn Cys Asn Cys 85 90 95 Ser Arg Cys Cys Trp SerLeu Pro Met His Phe Arg Tyr Ile Phe Asn 100 105 110 Ala Ser Leu Cys AsnCys Gln Arg Gln Gly Tyr Thr Leu Ser Cys Arg 115 120 125 Arg His Cys ThrAla Thr Lys Asn Ile Ser Phe Ser Phe Cys His Ile 130 135 140 Ser Phe ValPhe Leu Leu Lys Tyr Asp Pro Lys Asn Pro Gln Leu Arg 145 150 155 160 55405 PRT Drosophila melanogaster 55 Met Phe Asp Trp Val Gly Leu Leu LeuLys Val Leu Tyr Tyr Tyr Gly 1 5 10 15 Gln Ile Ile Gly Leu Ile Asn PheGlu Ile Asp Trp Gln Arg Gly Arg 20 25 30 Val Val Ala Ala Gln Arg Gly IleLeu Phe Ala Ile Ala Ile Asn Val 35 40 45 Leu Ile Cys Met Val Leu Leu LeuGln Ile Ser Lys Lys Phe Asn Leu 50 55 60 Asp Val Tyr Phe Gly Arg Ala AsnGln Leu His Gln Tyr Val Ile Ile 65 70 75 80 Val Met Val Ser Leu Arg MetAla Ser Leu Asn Arg Trp Arg Gln Arg 85 90 95 Ala Gln Leu Met Arg Leu ValGlu Cys Val Leu Arg Leu Phe Leu Lys 100 105 110 Lys Pro His Val Lys GlnMet Ser Arg Trp Ala Ile Leu Val Lys Phe 115 120 125 Ser Val Gly Val ValSer Asn Phe Leu Gln Met Ala Ile Ser Met Glu 130 135 140 Ser Leu Asp ArgLeu Gly Phe Asn Glu Phe Val Gly Met Ala Ser Asp 145 150 155 160 Phe TrpMet Ser Ala Ile Ile Asn Met Ala Ile Ser Gln His Tyr Leu 165 170 175 ValIle Leu Phe Val Arg Ala Tyr Tyr His Leu Leu Lys Thr Glu Val 180 185 190Arg Gln Ala Ile His Glu Ser Gln Met Leu Ser Glu Ile Tyr Pro Arg 195 200205 Arg Ala Ala Phe Met Thr Lys Cys Cys Tyr Leu Ala Asp Arg Ile Asp 210215 220 Asn Ile Ala Lys Leu Gln Asn Gln Leu Gln Ser Ile Val Thr Gln Leu225 230 235 240 Asn Gln Val Phe Gly Ile Gln Gly Ile Met Val Tyr Gly GlyTyr Tyr 245 250 255 Ile Phe Ser Val Ala Thr Thr Tyr Ile Thr Tyr Ser LeuAla Ile Asn 260 265 270 Gly Ile Glu Glu Leu His Leu Ser Val Arg Ala AlaAla Leu Val Phe 275 280 285 Ser Trp Phe Leu Phe Tyr Tyr Thr Ser Ala IleLeu Asn Leu Phe Val 290 295 300 Met Leu Lys Leu Phe Asp Asp His Lys GluMet Glu Arg Ile Leu Glu 305 310 315 320 Glu Arg Thr Leu Phe Thr Ser AlaLeu Asp Val Arg Leu Glu Gln Ser 325 330 335 Val Ser Phe Tyr Pro Thr IleThr Glu Leu Lys Tyr Arg Asp Leu Val 340 345 350 Leu Ser Gln Phe Glu SerIle Gln Leu Gln Leu Ile Arg Asn Pro Leu 355 360 365 Lys Ile Glu Val LeuAsp Ile Phe Thr Ile Thr Arg Ser Ser Ser Ala 370 375 380 Ala Met Ile GlySer Ile Ile Thr Asn Ser Ile Phe Leu Ile Gln Tyr 385 390 395 400 Asp MetGlu Tyr Phe 405 56 365 PRT Drosophila melanogaster 56 Met Trp Leu LeuArg Arg Ser Val Gly Lys Ser Gly Asn Arg Pro His 1 5 10 15 Asp Val TyrThr Cys Tyr Arg Leu Thr Ile Phe Met Ala Leu Cys Leu 20 25 30 Gly Ile ValPro Tyr Tyr Val Ser Ile Ser Ser Glu Gly Arg Gly Lys 35 40 45 Leu Thr SerSer Tyr Ile Gly Tyr Ile Asn Ile Ile Ile Arg Met Ala 50 55 60 Ile Tyr MetVal Asn Ser Phe Tyr Gly Ala Val Asn Arg Asp Thr Leu 65 70 75 80 Met SerAsn Phe Phe Leu Thr Asp Ile Ser Asn Val Ile Asp Ala Leu 85 90 95 Gln LysIle Asn Gly Met Leu Gly Ile Phe Ala Ile Leu Leu Ile Ser 100 105 110 LeuLeu Asn Arg Lys Glu Leu Leu Lys Leu Leu Ala Thr Phe Asp Arg 115 120 125Leu Glu Thr Glu Ala Phe Pro Arg Val Leu Lys Asn Leu Ala His Gln 130 135140 Trp Asp Thr Arg Ser Leu Lys Ala Val Asn Gln Lys Gln Arg Ser Leu 145150 155 160 Gln Cys Leu Asp Ser Phe Ser Met Tyr Thr Ile Val Thr Lys AspPro 165 170 175 Ala Glu Ile Ile Gln Glu Ser Met Glu Ile His His Leu IleCys Glu 180 185 190 Ala Ala Ala Thr Ala Asn Lys Tyr Phe Thr Tyr Gln LeuLeu Thr Ile 195 200 205 Ile Ser Ile Ala Phe Leu Ile Ile Val Phe Asp AlaTyr Tyr Val Leu 210 215 220 Glu Thr Leu Leu Gly Lys Ser Lys Arg Glu SerLys Phe Lys Thr Val 225 230 235 240 Glu Phe Val Thr Phe Phe Ser Cys GlnMet Ile Leu Tyr Leu Ile Ala 245 250 255 Ile Ile Ser Ile Val Glu Gly SerAsn Arg Ala Ile Lys Lys Ser Glu 260 265 270 Lys Thr Gly Gly Ile Val HisSer Leu Leu Asn Lys Thr Lys Ser Ala 275 280 285 Glu Val Lys Glu Lys LeuGln Gln Phe Ser Met Gln Leu Met His Leu 290 295 300 Lys Ile Asn Phe ThrAla Ala Gly Leu Phe Asn Ile Asp Arg Thr Leu 305 310 315 320 Tyr Phe ThrIle Ser Gly Ala Leu Thr Thr Tyr Leu Ile Ile Leu Leu 325 330 335 Gln PheThr Ser Asn Ser Pro Asn Asn Gly Tyr Gly Asn Gly Ser Ser 340 345 350 CysCys Glu Thr Phe Asn Asn Met Thr Asn His Thr Leu 355 360 365 57 450 PRTDrosophila melanogaster 57 Met Lys Gly Pro Asn Leu Asn Phe Arg Lys ThrPro Ser Lys Asp Asn 1 5 10 15 Gly Val Lys Gln Val Glu Ser Leu Ala ArgPro Glu Thr Pro Pro Pro 20 25 30 Lys Phe Val Glu Asp Ser Asn Leu Glu PheAsn Val Leu Ala Ser Glu 35 40 45 Lys Leu Pro Asn Tyr Thr Asn Leu Asp LeuPhe His Arg Ala Val Phe 50 55 60 Pro Phe Met Phe Leu Ala Gln Cys Val AlaIle Met Pro Leu Val Gly 65 70 75 80 Ile Arg Glu Ser Asn Pro Arg Arg ValArg Phe Ala Tyr Lys Ser Ile 85 90 95 Pro Met Phe Val Thr Leu Ile Phe MetIle Ala Thr Ser Ile Leu Phe 100 105 110 Leu Ser Met Phe Thr His Leu LeuLys Ile Gly Ile Thr Ala Lys Asn 115 120 125 Phe Val Gly Leu Val Phe PheGly Cys Val Leu Ser Ala Tyr Val Val 130 135 140 Phe Ile Arg Leu Ala LysLys Trp Pro Ala Val Val Arg Ile Trp Thr 145 150 155 160 Arg Thr Glu IlePro Phe Thr Lys Pro Pro Tyr Glu Ile Pro Lys Arg 165 170 175 Asn Leu SerArg Arg Val Gln Leu Ala Ala Leu Ala Ile Ile Gly Leu 180 185 190 Ser LeuGly Glu His Ala Leu Tyr Gln Val Ser Ala Ile Leu Ser Tyr 195 200 205 ThrArg Arg Ile Gln Met Cys Ala Asn Ile Thr Thr Val Pro Ser Phe 210 215 220Asn Asn Tyr Met Gln Thr Asn Tyr Asp Tyr Val Phe Gln Leu Leu Pro 225 230235 240 Tyr Ser Pro Ile Ile Ala Val Leu Ile Leu Ala Thr Cys Thr Phe Val245 250 255 Trp Asn Tyr Met Asp Leu Phe Ile Met Met Ile Ser Lys Gly LeuSer 260 265 270 Tyr Arg Phe Glu Gln Ile Thr Thr Arg Ile Arg Lys Leu GluHis Glu 275 280 285 Glu Val Cys Glu Ser Val Phe Ile Gln Ile Arg Glu HisTyr Val Lys 290 295 300 Met Cys Glu Leu Leu Glu Phe Val Asp Ser Ala MetSer Ser Leu Ile 305 310 315 320 Leu Leu Ser Cys Val Asn Asn Leu Tyr PheVal Cys Tyr Gln Leu Leu 325 330 335 Asn Val Phe Asn Lys Leu Arg Trp ProIle Asn Tyr Ile Tyr Phe Trp 340 345 350 Tyr Ser Leu Leu Tyr Leu Ile GlyArg Thr Ala Phe Val Phe Leu Thr 355 360 365 Ala Ala Asp Ile Asn Glu GluSer Lys Arg Gly Leu Gly Val Leu Arg 370 375 380 Arg Val Ser Ser Arg SerTrp Cys Val Glu Val Glu Arg Leu Ile Phe 385 390 395 400 Gln Met Thr ThrGln Thr Val Ala Leu Ser Gly Lys Lys Phe Tyr Phe 405 410 415 Leu Thr ArgArg Leu Leu Phe Gly Met Ala Gly Thr Ile Val Thr Tyr 420 425 430 Glu LeuVal Leu Leu Gln Phe Asp Glu Pro Asn Arg Arg Lys Gly Leu 435 440 445 GlnPro 450 58 28 PRT Drosophila melanogaster 58 Ile Tyr Ile Leu Ser Leu TyrIle Phe Phe Gln Phe Ile Ser Asn Val 1 5 10 15 Ser Leu Ile Val Val LeuLys Leu Phe Arg Asp Ile 20 25 59 444 PRT Drosophila melanogaster 59 MetArg Gln Leu Lys Gly Arg Asn Arg Cys Asn Arg Ala Val Arg His 1 5 10 15Leu Lys Val Gln Gly Lys Met Trp Leu Lys Asn Leu Lys Ser Gly Leu 20 25 30Glu Gln Ile Arg Glu Ser Gln Val Arg Gly Thr Arg Lys Asn Phe Leu 35 40 45His Asp Gly Ser Phe His Glu Ala Val Ala Pro Val Leu Ala Val Ala 50 55 60Gln Cys Phe Cys Leu Met Pro Val Cys Gly Ile Ser Ala Pro Thr Tyr 65 70 7580 Arg Gly Leu Ser Phe Asn Arg Arg Ser Trp Arg Phe Trp Tyr Ser Ser 85 9095 Leu Tyr Leu Cys Ser Thr Ser Val Asp Leu Ala Phe Ser Ile Arg Arg 100105 110 Val Ala His Ser Val Leu Asp Val Arg Ser Val Glu Pro Ile Val Phe115 120 125 His Val Ser Ile Leu Ile Ala Ser Trp Gln Phe Leu Asn Leu AlaGln 130 135 140 Leu Trp Pro Gly Leu Met Arg His Trp Ala Ala Val Glu ArgArg Leu 145 150 155 160 Pro Gly Tyr Thr Cys Cys Leu Gln Arg Ala Arg ProAla Arg Arg Leu 165 170 175 Lys Leu Val Ala Phe Val Leu Leu Val Val SerLeu Met Glu His Leu 180 185 190 Leu Ser Ile Ile Ser Val Val Tyr Tyr AspPhe Cys Pro Arg Arg Ser 195 200 205 Asp Pro Val Glu Ser Tyr Leu Leu GlyAla Ser Ala Gln Leu Phe Glu 210 215 220 Val Phe Pro Tyr Ser Asn Trp LeuAla Trp Leu Gly Lys Ile Gln Asn 225 230 235 240 Val Leu Leu Thr Phe GlyTrp Ser Tyr Met Asp Ile Phe Leu Met Met 245 250 255 Leu Gly Met Gly LeuSer Glu Met Leu Ala Arg Leu Asn Arg Ser Leu 260 265 270 Glu Gln Gln ValArg Gln Pro Met Pro Glu Ala Tyr Trp Thr Trp Ser 275 280 285 Arg Thr LeuTyr Arg Ser Ile Val Glu Leu Ile Arg Glu Val Asp Asp 290 295 300 Ala ValSer Gly Ile Met Leu Ile Ser Phe Gly Ser Asn Leu Tyr Phe 305 310 315 320Ile Cys Leu Gln Leu Leu Lys Ser Ile Asn Thr Met Pro Ser Ser Ala 325 330335 His Ala Val Tyr Phe Tyr Phe Ser Leu Leu Phe Leu Leu Ser Arg Ser 340345 350 Thr Ala Val Leu Leu Phe Val Ser Ala Ile Asn Asp Gln Ala Arg Glu355 360 365 Pro Leu Arg Leu Leu Arg Leu Val Pro Leu Lys Gly Tyr His ProGlu 370 375 380 Val Phe Arg Phe Ala Ala Glu Leu Ala Ser Asp Gln Val AlaLeu Thr 385 390 395 400 Gly Leu Lys Phe Phe Asn Val Thr Arg Lys Leu PheLeu Ala Met Ala 405 410 415 Gly Thr Val Ala Thr Tyr Glu Leu Val Leu IleGln Phe His Glu Asp 420 425 430 Lys Lys Thr Trp Asp Cys Ser Pro Phe AsnLeu Asp 435 440 60 25 PRT Artificial sequence motif 60 Gly Xaa Phe XaaXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 1 5 10 15 Xaa Thr TyrLeu Xaa Leu Xaa Gln Phe 20 25 61 33 PRT Drosophila melanogaster 61 PheArg Phe Gln Leu Cys Gly Leu Phe Ser Ile Asn His Asn Met Gly 1 5 10 15Phe Gln Met Ile Ile Thr Ser Phe Leu Tyr Leu Val Tyr Leu Leu Gln 20 25 30Phe 62 33 PRT Drosophila melanogaster 62 Leu Gln Leu Trp Ser Cys Gly LeuPhe Gln Ala Asn Arg Ser Met Trp 1 5 10 15 Phe Ala Met Ile Ser Ser ValLeu Tyr Tyr Ile Leu Val Leu Leu Gln 20 25 30 Phe 63 33 PRT Drosophilamelanogaster 63 Ser Thr Tyr Lys Val Cys Gly Leu Phe Ile Phe Asn Lys GlnThr Ser 1 5 10 15 Leu Ala Tyr Phe Phe Tyr Val Leu Val Gln Val Leu ValLeu Val Gln 20 25 30 Phe 64 33 PRT Drosophila melanogaster 64 His GluPhe Tyr Val Met Gly Leu Phe Lys Met Glu Arg Gly Arg Leu 1 5 10 15 IleAla Met Leu Ser Ser Val Ile Thr His Thr Met Val Leu Val Gln 20 25 30 Trp65 33 PRT Drosophila melanogaster 65 Leu Glu Ile Lys Val Leu Gly Phe PheHis Leu Asn Asn Glu Phe Ile 1 5 10 15 Leu Leu Ile Leu Ser Ala Ile IleSer Tyr Leu Phe Ile Leu Ile Gln 20 25 30 Phe 66 33 PRT Drosophilamelanogaster 66 Pro Ile Met Asn Leu Asp Gly Tyr Ala Asn Ile Asn Arg GluLeu Ile 1 5 10 15 Thr Thr Asn Ile Ser Phe Met Ala Thr Tyr Leu Val ValLeu Leu Gln 20 25 30 Phe 67 33 PRT Drosophila melanogaster 67 Ser ThrIle Asn Cys Gly Gly Phe Phe Asp Val Asn Arg Thr Leu Phe 1 5 10 15 LysGly Leu Leu Thr Thr Met Val Thr Tyr Leu Val Val Leu Leu Gln 20 25 30 Phe68 33 PRT Drosophila melanogaster 68 Leu Ala Ile Asn Ala Glu Gly Phe MetSer Thr Asp Asn Ser Leu Leu 1 5 10 15 Met Ser Ile Leu Ala Ala Lys ValThr Tyr Leu Ile Val Leu Met Gln 20 25 30 Phe 69 33 PRT Drosophilamelanogaster 69 Ile Asn Phe Thr Ala Ala Gly Leu Phe Asn Ile Asp Arg ThrLeu Tyr 1 5 10 15 Phe Thr Ile Ser Gly Ala Leu Thr Thr Tyr Leu Ile IleLeu Leu Gln 20 25 30 Phe 70 33 PRT Drosophila melanogaster 70 Leu HisPhe Ser Ala Ala Gly Phe Phe Asn Val Asp Cys Thr Leu Leu 1 5 10 15 TyrThr Ile Val Gly Ala Thr Thr Thr Tyr Leu Ile Ile Leu Ile Gln 20 25 30 Phe71 33 PRT Drosophila melanogaster 71 Ala Asp Phe Ser Ala Cys Gly Leu CysArg Val Asn Arg Thr Ile Leu 1 5 10 15 Thr Ser Phe Ala Ser Ala Ile AlaThr Tyr Leu Val Ile Leu Ile Gln 20 25 30 Phe 72 32 PRT Drosophilamelanogaster 72 Phe Met Thr Cys Ala Ala Ser Phe Met Ser Asn Arg Val ThrIle Gln 1 5 10 15 Val Cys Leu Lys Ala Ile Phe Thr Tyr Met Val Ile LeuVal Gln Phe 20 25 30 73 33 PRT Drosophila melanogaster 73 Val Ala LeuThr Gly Met Lys Phe Phe His Leu Thr Arg Lys Leu Val 1 5 10 15 Leu SerVal Ala Gly Thr Ile Val Thr Tyr Glu Leu Val Leu Ile Gln 20 25 30 Phe 7433 PRT Drosophila melanogaster 74 Val Ala Leu Thr Gly Leu Lys Phe PheAsn Val Thr Arg Lys Leu Phe 1 5 10 15 Leu Ala Met Ala Gly Thr Val AlaThr Tyr Glu Leu Val Leu Ile Gln 20 25 30 Phe 75 33 PRT Drosophilamelanogaster 75 Met Ser Ile Ser Gly Ala Lys Phe Phe Thr Val Ser Leu AspLeu Phe 1 5 10 15 Ala Ser Val Leu Gly Ala Val Val Thr Tyr Phe Met ValLeu Val Gln 20 25 30 Leu 76 33 PRT Drosophila melanogaster 76 Val GluLeu Asn Ala Met Gly Tyr Leu Ser Ile Ser Leu Asp Thr Phe 1 5 10 15 LysGln Leu Met Ser Val Ser Tyr Arg Val Ile Thr Met Leu Met Gln 20 25 30 Met77 33 PRT Drosophila melanogaster 77 Ile Thr Leu Thr Ala Gly Gly Val PhePro Ile Ser Met Gln Thr Asn 1 5 10 15 Leu Ala Met Val Lys Leu Ala PheSer Val Val Thr Val Ile Lys Gln 20 25 30 Phe 78 33 PRT Drosophilamelanogaster 78 Ile Ile Leu Thr Ala Gly Gly Val Phe Pro Ile Ser Met GlnThr Asn 1 5 10 15 Leu Asn Met Val Lys Leu Ala Phe Thr Val Val Thr IleVal Lys Gln 20 25 30 Phe 79 33 PRT Drosophila melanogaster 79 Ile ValPhe Ile Ala Gly Gly Ile Phe Gln Ile Ser Met Ser Ser Asn 1 5 10 15 IleSer Val Ala Lys Phe Ala Phe Ser Val Ile Thr Ile Thr Lys Gln 20 25 30 Met80 33 PRT Drosophila melanogaster 80 Ile Ile Phe Ile Ala Gly Gly Ile PhePro Ile Ser Met Asn Ser Asn 1 5 10 15 Ile Thr Val Ala Lys Phe Ala PheSer Ile Ile Thr Ile Val Arg Gln 20 25 30 Met 81 33 PRT Drosophilamelanogaster 81 Ile Gln Phe Thr Ala Gly Ser Thr Phe Pro Ile Ser Val GlnSer Asn 1 5 10 15 Ile Ala Val Ala Lys Phe Ala Phe Thr Ile Ile Thr IleVal Asn Gln 20 25 30 Met 82 33 PRT Drosophila melanogaster 82 Ile AlaPhe Thr Ala Gly Ser Ile Phe Pro Ile Ser Thr Gly Ser Asn 1 5 10 15 IleLys Val Ala Lys Leu Ala Phe Ser Val Val Thr Phe Val Asn Gln 20 25 30 Leu83 33 PRT Drosophila melanogaster 83 Ile Leu Phe Thr Ala Gly Gly Ile PhePro Ile Cys Leu Asn Thr Asn 1 5 10 15 Ile Lys Met Ala Lys Phe Ala PheSer Val Val Thr Ile Val Asn Glu 20 25 30 Met 84 33 PRT Drosophilamelanogaster 84 Ile Thr Leu Thr Ala Met Lys Leu Phe Pro Ile Asn Leu AlaThr Tyr 1 5 10 15 Phe Ser Ile Ala Lys Phe Ser Phe Ser Leu Tyr Thr LeuIle Lys Gly 20 25 30 Met 85 33 PRT Drosophila melanogaster 85 Ile ArgIle Asp Cys Leu Gly Leu Thr Ile Leu Asp Cys Ser Leu Leu 1 5 10 15 ThrArg Met Ala Cys Ser Val Gly Thr Tyr Met Ile Tyr Ser Ile Gln 20 25 30 Phe86 33 PRT Drosophila melanogaster 86 Phe Gln Phe Asn Gly Val Gly Leu PheAla Leu Asp Tyr Thr Phe Ile 1 5 10 15 Phe Ser Thr Val Ser Ala Ala ThrSer Tyr Leu Ile Val Leu Leu Gln 20 25 30 Phe 87 33 PRT Drosophilamelanogaster 87 Val Asp Phe Ser Ala Cys Gly Phe Phe Thr Leu Asp Met GluThr Leu 1 5 10 15 Tyr Gly Val Ser Gly Gly Ile Thr Ser Tyr Leu Ile IleLeu Ile Gln 20 25 30 Phe 88 32 PRT Drosophila melanogaster 88 Pro ProMet Leu Cys Gly Leu Leu His Leu Asp Arg Arg Leu Val Tyr 1 5 10 15 LeuIle Ala Val Thr Ala Phe Ser Tyr Phe Ile Thr Leu Val Gln Phe 20 25 30 8933 PRT Drosophila melanogaster 89 Tyr Gln Ile Lys Pro Leu Gly Leu TyrGlu Leu Asp Met Arg Leu Ile 1 5 10 15 Ser Asn Val Phe Ser Ala Val AlaSer Phe Leu Leu Ile Leu Val Gln 20 25 30 Ala 90 33 PRT Drosophilamelanogaster 90 Ile Gln Phe Thr Ser Gly Leu Asp Val Val Leu Ser Arg LysVal Ile 1 5 10 15 Gly Leu Phe Thr Ser Ile Leu Val Asn Tyr Leu Leu IleLeu Ile Gln 20 25 30 Phe 91 33 PRT Drosophila melanogaster 91 Gln ProLeu Glu Ala Cys Gly Ile Val Thr Leu Asp Thr Arg Ser Leu 1 5 10 15 GlyGly Phe Ile Gly Val Leu Met Ala Ile Val Ile Phe Leu Ile Gln 20 25 30 Ile92 31 PRT Drosophila melanogaster 92 Phe Arg Ile Thr Gly Tyr Phe Phe GluAla Asn Met Glu Ala Phe Ser 1 5 10 15 Ser Ile Val Arg Thr Ala Met SerTyr Ile Thr Met Leu Arg Ser 20 25 30 93 31 PRT Drosophila melanogaster93 Cys Gln Met Lys Gly Tyr Phe Phe Glu Ala Ser Met Ala Thr Phe Ser 1 510 15 Thr Ile Val Arg Ser Ala Val Ser Tyr Ile Met Met Leu Arg Ser 20 2530 94 31 PRT Drosophila melanogaster 94 Met Lys Met Arg Ala Leu Leu ValAsp Leu Asn Leu Arg Thr Phe Ile 1 5 10 15 Asp Ile Gly Arg Gly Ala TyrSer Tyr Phe Asn Leu Leu Arg Ser 20 25 30 95 31 PRT Drosophilamelanogaster 95 Ala Lys Ile Phe Gly Phe Met Phe Val Val Asp Leu Pro LeuLeu Leu 1 5 10 15 Trp Val Ile Arg Thr Ala Gly Ser Phe Leu Ala Met LeuArg Thr 20 25 30 96 32 PRT Drosophila melanogaster 96 Leu Ala Ser LeuVal Gly Gly Thr Tyr Pro Met Asn Leu Lys Met Leu 1 5 10 15 Gln Ser LeuLeu Asn Ala Ile Tyr Ser Phe Phe Thr Leu Leu Arg Arg 20 25 30 97 32 PRTDrosophila melanogaster 97 Asn Glu Ile Arg Val Gly Asn Val Tyr Pro MetThr Leu Ala Met Phe 1 5 10 15 Gln Ser Leu Leu Asn Ala Ser Tyr Ser TyrPhe Thr Met Leu Arg Gly 20 25 30 98 32 PRT Drosophila melanogaster 98Ala Ala Ile Leu Leu Gly Asn Ile Arg Pro Ile Thr Leu Glu Leu Phe 1 5 1015 Gln Asn Leu Leu Asn Thr Thr Tyr Thr Phe Phe Thr Val Leu Lys Arg 20 2530 99 32 PRT Drosophila melanogaster 99 Gln Leu Leu Leu Ala Gly Asn LeuVal Pro Ile His Leu Ser Thr Tyr 1 5 10 15 Val Ala Cys Trp Lys Gly AlaTyr Ser Phe Phe Thr Leu Met Ala Asp 20 25 30 100 32 PRT Drosophilamelanogaster 100 Ser Leu Ile Tyr Ala Gly Asn Tyr Ile Ala Leu Ser Leu GluThr Phe 1 5 10 15 Glu Gln Val Met Arg Phe Thr Tyr Ser Val Phe Thr LeuLeu Leu Arg 20 25 30 101 32 PRT Drosophila melanogaster 101 Val Asn IleLys Ala Gly Gly Ile Val Gly Ile Asp Met Ser Ala Phe 1 5 10 15 Phe AlaThr Val Arg Met Ala Tyr Ser Phe Tyr Thr Leu Ala Leu Ser 20 25 30 102 32PRT Drosophila melanogaster 102 Val Gln Ile Lys Ala Gly Gly Met Ile GlyIle Gly Met Asn Ala Phe 1 5 10 15 Phe Ala Thr Val Arg Leu Ala Tyr SerPhe Phe Thr Leu Ala Met Ser 20 25 30 103 32 PRT Drosophila melanogaster103 Trp Ile Ile Lys Ala Gly Gly Leu Ile Glu Leu Asn Leu Asn Ala Phe 1 510 15 Phe Ala Thr Leu Lys Met Ala Tyr Ser Leu Phe Ala Val Val His Arg 2025 30 104 32 PRT Drosophila melanogaster 104 Ser Thr Ala Val Ala Gly GlyMet Met Arg Ile His Leu Asp Thr Phe 1 5 10 15 Phe Ser Thr Leu Lys GlyAla Tyr Ser Leu Phe Thr Ile Ile Ile Arg 20 25 30 105 32 PRT Drosophilamelanogaster 105 Val Thr Ile Arg Ala Gly Asn Ser Phe Ala Val Gly Leu ProIle Phe 1 5 10 15 Val Lys Thr Ile Asn Asn Ala Tyr Ser Phe Leu Ala LeuLeu Leu Asn 20 25 30 106 32 PRT Drosophila melanogaster 106 Val Lys ValArg Ala Gly Val Phe Phe Glu Ile Gly Leu Pro Ile Phe 1 5 10 15 Val LysThr Ile Asn Asn Ala Tyr Ser Phe Phe Ala Leu Leu Leu Lys 20 25 30 107 33PRT Drosophila melanogaster 107 Val Thr Leu Lys Ala Gly Gly Phe Phe HisIle Gly Leu Pro Leu Phe 1 5 10 15 Thr Lys Val Val Phe Ser Thr Leu GluAsn Pro Cys Ile Ser Tyr Leu 20 25 30 Tyr 108 32 PRT Drosophilamelanogaster 108 Val Ser Met Ala Val Pro Phe Phe Ser Pro Ser Leu Ala ThrPhe Ala 1 5 10 15 Ala Ile Leu Gln Thr Ser Gly Ser Ile Ile Ala Leu ValLys Ser Phe 20 25 30 109 33 PRT Drosophila melanogaster 109 Leu Met TyrVal Ala Glu Pro Phe Leu Pro Phe Thr Leu Gly Thr Tyr 1 5 10 15 Met LeuVal Leu Lys Asn Cys Tyr Arg Leu Leu Ala Leu Met Gln Glu 20 25 30 Ser 11033 PRT Drosophila melanogaster 110 Phe Phe Ile Thr Gly Leu Asn Tyr PheArg Val Ser Leu Thr Ala Val 1 5 10 15 Leu Lys Ile Ile Gln Gly Ala PheSer Tyr Phe Thr Phe Leu Asn Ser 20 25 30 Met 111 33 PRT Drosophilamelanogaster 111 Gln Gln Leu Gly Ala Phe Gly Leu Ile Gln Val Asn Met ValHis Phe 1 5 10 15 Thr Glu Ile Met Gln Leu Ala Tyr Arg Leu Phe Thr PheLeu Lys Ser 20 25 30 His 112 33 PRT Drosophila melanogaster 112 Val HisVal Thr Ala Gly Lys Phe Tyr Val Met Asp Val Asn Arg Leu 1 5 10 15 ArgSer Val Ile Thr Gln Ala Phe Ser Phe Leu Thr Leu Leu Gln Lys 20 25 30 Leu113 33 PRT Drosophila melanogaster 113 His Asn Ile Gln Ile Leu Gly ValMet Ser Leu Ser Val Arg Thr Ala 1 5 10 15 Leu Gln Ile Val Lys Leu IleTyr Ser Val Ser Met Met Met Met Asn 20 25 30 Arg 114 33 PRT Drosophilamelanogaster 114 Lys Arg Val Val Leu Leu Asn Val Phe Thr Phe Asp Arg LysLeu Thr 1 5 10 15 Leu Thr Leu Leu Ala Lys Ser Thr Leu Tyr Thr Ile CysCys Leu Gln 20 25 30 Asn 115 33 PRT Drosophila melanogaster 115 Arg GlnHis Val Val Cys Gly Val Ile Asn Leu Asp Leu Lys Phe Leu 1 5 10 15 ThrThr Leu Leu Val Ala Ser Ala Asp Phe Phe Ile Phe Leu Leu Gln 20 25 30 Tyr116 28 PRT Drosophila melanogaster 116 Thr Val Leu Gly Ala Tyr Phe PheGlu Leu Gly Arg Pro Leu Leu Val 1 5 10 15 Trp Val Ser Ile Phe Leu PheIle Val Leu Leu Phe 20 25

What is claimed is:
 1. An isolated nucleic acid encoding an insectgustatory receptor protein, wherein the receptor protein comprises seventransmembrane domains and a C-terminal domain, and the C-terminal domaincomprises consecutive amino acids having the following sequence:-G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQ ID NO:60), where X is any amino acid, and / means or.
 2. An isolated nucleicacid encoding an insect odorant receptor protein, wherein the receptorprotein comprises seven transmembrane domains and a C-terminal domain,and the C-terminal domain comprises consecutive amino acids having thefollowing sequence:-G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQ ID NO:60), where X is any amino acid, and / means or.
 3. An isolated nucleicacid encoding an insect gustatory receptor protein, wherein the nucleicacid molecule encodes a protein selected from the group consisting of:(a) an insect receptor protein comprising consecutive amino acids havinga sequence identical to that set forth for Gr2B1 in SEQ ID NO: 1, (b) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr8D1 in SEQ ID NO: 2, (c) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr10B1 in SEQ ID NO: 3, (d) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr10B2 in SEQ ID NO: 4, (e) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr28A2 in SEQ ID NO: 5, (f) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr28A4 in SEQ ID NO: 6, (g) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr33C1 in SEQ ID NO: 7, (h) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr36B2 in SEQ ID NO: 8, (i) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr36B3 in SEQ ID NO: 9, (j) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr59C1 in SEQ ID NO: 10, (k) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr6D1 in SEQ ID NO: 11, (l) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr63F1 in SEQ ID NO: 12, (m) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr64A2 in SEQ ID NO: 13, (n) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for GR64A3 in SEQ ID NO: 14, (o) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr66C1 in SEQ ID NO: 15, (p) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr92D1 in SEQ ID NO: 16, (q) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr98A1in SEQ ID NO: 17, (r) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr98A2 in SEQ ID NO: 18, (s) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr2940.1 in SEQ ID NO: 19, (t)an insect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr2940.2 in SEQ ID NO: 20, (u)an insect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr2940.3 in SEQ ID NO: 21, (v)an insect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr2940.4 in SEQ ID NO: 22, (w)an insect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr2940.5 in SEQ ID NO: 23, (x)an insect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr57B1 in SEQ ID NO: 46, (y) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr93F1 in SEQ ID NO: 48, (z) aninsect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr93F2 in SEQ ID NO: 49, (aa)an insect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr93F3 in SEQ ID NO: 50, (bb)an insect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr93F4 in SEQ ID NO: 51, (cc)an insect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr94E1 in SEQ ID NO: 52, (dd)an insect receptor protein comprising consecutive amino acids having asequence identical to that set forth for Gr93D1 in SEQ ID NO: 53, (ee)an insect receptor protein comprising consecutive amino acids having asequence identical to that set forth for GrLU1=Gr36B1 in SEQ ID NO: 55,(ff) an insect receptor protein comprising consecutive amino acidshaving a sequence identical to that set forth for GrLU2=Gr28A3 in SEQ IDNO: 56, (gg) an insect receptor protein comprising consecutive aminoacids having a sequence identical to that set forth for GrLU3=Gr64A1 inSEQ ID NO: 57, (hh) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth forGrLU7=Gr5A1 in SEQ ID NO: 59, and (ii) an insect gustatory receptorprotein which shares from 7-50% amino acid identity with any one of theproteins of (a)-(hh), and comprises seven transmembrane domains and aC-terminal domain, wherein the C-terminal domain comprises consecutiveamino acids having the following sequence:-G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQ ID NO:60), where X is any amino acid, and / means or.
 4. An isolated nucleicacid molecule encoding an insect odorant receptor protein, wherein thenucleic acid molecule encodes a protein selected from the groupconsisting of: (a) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr2B1 inSEQ ID NO: 1, (b) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr8D1 inSEQ ID NO: 2, (c) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr10B1 inSEQ ID NO: 3, (d) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr10B2 inSEQ ID NO: 4, (e) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr28A2 inSEQ ID NO: 5, (f) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr28A4 inSEQ ID NO: 6, (g) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr33C1 inSEQ ID NO: 7, (h) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr36B2 inSEQ ID NO: 8, (i) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr36B3 inSEQ ID NO: 9, (j) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr59C1 inSEQ ID NO: 10, (k) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr61D1 inSEQ ID NO: 11, (l) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr63F1 inSEQ ID NO: 12, (m) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr64A2 inSEQ ID NO: 13, (n) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for GR64A3 inSEQ ID NO: 14, (o) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr66C1 inSEQ ID NO: 15, (p) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr92D1 inSEQ ID NO: 16, (q) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr98A1 inSEQ ID NO: 17, (r) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr98A2 inSEQ ID NO: 18, (s) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr2940.1in SEQ ID NO: 19, (t) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr2940.2in SEQ ID NO: 20, (u) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr2940.3in SEQ ID NO: 21, (v) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr2940.4in SEQ ID NO: 22, (w) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr2940.5in SEQ ID NO: 23, (x) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr57B1 inSEQ ID NO: 46, (y) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr93F1 inSEQ ID NO: 48, (z) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr93F2 inSEQ ID NO: 49, (aa) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr93F3 inSEQ ID NO: 50, (bb) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr93F4 inSEQ ID NO: 51, (cc) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr94E1 inSEQ ID NO: 52, (dd) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth for Gr93D1 inSEQ ID NO: 53, (ee) an insect receptor protein comprising consecutiveamino acids having a sequence identical to that set forth forGrLU1=Gr36B1 in SEQ ID NO: 55, (ff) an insect receptor proteincomprising consecutive amino acids having a sequence identical to thatset forth for GrLU2=Gr28A3 in SEQ ID NO: 56, (gg) an insect receptorprotein comprising consecutive amino acids having a sequence identicalto that set forth for GrLU3=Gr64A1 in SEQ ID NO: 57, (hh) an insectreceptor protein comprising consecutive amino acids having a sequenceidentical to that set forth for GrLU7=Gr5A1 in SEQ ID NO: 59, and (ii)an insect odorant receptor protein which shares from 7-50% amino acididentity with any one of the proteins of (a), and comprises seventransmembrane domains and a C-terminal domain, wherein the C-terminaldomain comprises consecutive amino acids having the following sequence:-G-L/F-F-X-X-X-X-X-X-X-X-X-X-X-X-X-X-T-Y-L-V/I-L-V/I/L-Q-F- (SEQ ID NO:60), where X is any amino acid, and / means or.
 5. The isolated nucleicacid of claim 1, 2, 3, or 4, wherein the nucleic acid is DNA or RNA. 6.The isolated nucleic acid of claim 6, wherein the DNA is cDNA, genomicDNA, or synthetic DNA.
 7. The isolated nucleic acid of claim 1, 2, 3, or4, wherein the nucleic acid is a Drosophila receptor.
 8. A nucleic acidcomprising at least 12 nucleotides which specifically hybridizes withthe isolated nucleic acid of claim 1, 2, 3, or
 4. 9. The nucleic acid ofclaim 8, wherein the nucleic acid is DNA, cDNA, genomic DNA, syntheticDNA, RNA or synthetic RNA.
 10. A vector which comprises the isolatednucleic acid of claim 1, 2, 3, or
 4. 11. The vector of claim 10, whereinthe isolated nucleic acid is operatively linked to a regulatory element.12. The vector of claim 11, wherein the vector is a plasmid.
 13. A hostvector system for production of a polypeptide having the biologicalactivity of an insect gustatory receptor, which comprises the vector ofclaim 10 and a suitable host.
 14. A host vector system for production ofa polypeptide having the biological activity of an insect odorantreceptor, which comprises the vector of claim 10 and a suitable host.15. The host vector system of claim 13 or 14, wherein the suitable hostis a bacterial cell, a yeast cell, an insect cell, or an animal cell.16. A method of producing a polypeptide having the biological activityof an insect gustatory receptor which comprising growing the host vectorsystem of claim 13 under conditions permitting production of thepolypeptide and recovering the polypeptide so produced.
 17. A method ofproducing a polypeptide having the biological activity of an insectodorant receptor which comprising growing the host vector system ofclaim 14 under conditions permitting production of the polypeptide andrecovering the polypeptide so produced.
 18. A purified insect gustatoryreceptor protein encoded by the isolated nucleic acid of claim 1 or 3.19. A purified insect odorant receptor protein encoded by the isolatednucleic acid of claim 2 or
 4. 20. An antibody which specifically bindsto an insect receptor protein encoded by the isolated nucleic acid ofclaim 1, 2, 3, or
 4. 21. An antibody which competitively inhibits thebinding of the antibody of claim
 20. 22. The antibody of claim 20 or 21,wherein the antibody is a monoclonal antibody.
 23. A method oftransforming a cell which comprises transfecting a host cell with thevector of claim
 10. 24. A transformed cell produced by the method ofclaim
 23. 25. The transformed cell of claim 24, wherein prior to beingtransfected with the vector the host cell does not express a gustatoryreceptor protein.
 26. The transformed cell of claim 24, wherein prior tobeing transfected with the vector the host cell does not express anodorant receptor protein.
 27. A method of identifying a compound whichspecifically binds to an insect gustatory receptor which comprisescontacting the transformed cell of claim 24, or a membrane fraction fromsaid cells, with the compound under conditions permitting binding of thecompound to the gustatory receptor, detecting the presence of any suchcompound specifically bound to the receptor, and thereby identifying thecompound as a compound which specifically binds to an insect gustatoryreceptor.
 28. A method of identifying a compound which specificallybinds to an insect odorant receptor which comprises contacting thetransformed cell of claim 24, or a membrane fraction from said cells,with the compound under conditions permitting binding of the compound tothe odorant receptor, detecting the presence of any such compoundspecifically bound to the receptor, and thereby identifying the compoundas a compound which specifically binds to an insect odorant receptor.29. A method of identifying a compound which specifically binds to aninsect gustatory receptor which comprises contacting the purified insectgustatory receptor protein of claim 18 with the compound underconditions permitting binding of the compound to the purified gustatoryreceptor protein, detecting the presence of any such compoundspecifically bound to the receptor, and thereby identifying the compoundas a compound which specifically binds to an insect gustatory receptor.30. A method of identifying a compound which specifically binds to aninsect odorant receptor which comprises contacting the purified insectodorant receptor protein of claim 19 with the compound under conditionspermitting binding of the compound to the purified odorant receptorprotein, detecting the presence of any such compound specifically boundto the receptor, and thereby identifying the compound as a compoundwhich specifically binds to an insect odorant receptor.
 31. The methodof claim 29 or 30, wherein the purified insect receptor protein isembedded in a lipid bilayer.
 32. A method of identifying a compoundwhich activates an insect gustatory receptor which comprises contactingthe transformed cell of claim 24, or a membrane fraction from saidcells, with the compound under conditions permitting activation of thegustatory receptor, detecting activation of the receptor, and therebyidentifying the compound as a compound which activates an insectgustatory receptor.
 33. A method of identifying a compound whichactivates an insect odorant receptor which comprises contacting thetransformed cell of claim 24, or a membrane fraction from said cells,with the compound under conditions permitting activation of the odorantreceptor, detecting activation of the receptor, and thereby identifyingthe compound as a compound which activates an insect odorant receptor.34. A method of identifying a compound which activates an insectgustatory receptor which comprises contacting the purified insectgustatory receptor protein of claim 18 with the compound underconditions permitting activation of the gustatory receptor, detectingactivation of the receptor, and thereby identify the compound as acompound which activates an insect gustatory receptor.
 35. A method ofidentifying a compound which activates an insect odorant receptor whichcomprises contacting the purified insect odorant receptor protein ofclaim 19 with the compound under conditions permitting activation of theodorant receptor, detecting activation of the receptor, and therebyidentify the compound as a compound which activates an insect odorantreceptor.
 36. The method of claim 34 or 35, wherein the purified insectreceptor protein is embedded in a lipid bilayer.
 37. A method ofidentifying a compound which inhibits the activity of an insectgustatory receptor which comprises contacting the transformed cell ofclaim 24, or a membrane fraction from said cells, with the compoundunder conditions permitting inhibition of the activity of the gustatoryreceptor, detecting inhibition of the activity of the receptor, andthereby identifying the compound as a compound which inhibits theactivity of an insect gustatory receptor.
 38. A method of identifying acompound which inhibits the activity of an insect odorant receptor whichcomprises contacting the transformed cell of claim 24, or a membranefraction from said cells, with the compound under conditions permittinginhibition of the activity of the odorant receptor, detecting inhibitionof the activity of the receptor, and thereby identifying the compound asa compound which inhibits the activity of an insect odorant receptor.39. A method of identifying a compound which inhibits the activity of aninsect gustatory receptor which comprises contacting the purified insectgustatory receptor protein of claim 18 with the compound underconditions permitting inhibition of the activity of the gustatoryreceptor, detecting inhibition of the activity of the receptor, andthereby identifying the compound as a compound which inhibits theactivity of an insect gustatory receptor.
 40. A method of identifying acompound which inhibits the activity of an insect odorant receptor whichcomprises contacting the purified insect odorant receptor protein ofclaim 19 with the compound under conditions permitting inhibition of theactivity of the odorant receptor, detecting inhibition of the activityof the receptor, and thereby identifying the compound as a compoundwhich inhibits the activity of an insect odorant receptor.
 41. Themethod of claim 39 or 40, wherein the purified insect receptor proteinis embedded in a lipid bilayer.
 42. The method of any one of claims27-30, 32-35, or 37-40, wherein the compound is not previously known.43. A compound identified by the method of claim
 42. 44. The compound ofclaim 43, wherein the compound is an alarm odorant ligand.
 45. Thecompound of claim 43, wherein the compound is a ligand associated withfertility.
 46. The compound of claim 43, wherein the compound thecompound interferes with chemosensory perception.
 47. A method ofcombating ingestion of crops by pest insects which comprises identifyinga compound by the method of any one of claims 27-30, 32-35, or 37-40,and spraying the crops with the compound.
 48. A method of combatingdisease-carrying insects in an area which comprises identifying acompound by the method of any one of claims 27-30, 32-35, or 37-40, andspraying the area with the compound.
 49. A method of controlling a pestpopulation in an area which comprises identifying a compound by themethod of any one of claims 27-30, 32-35, or 37-40, and spraying thearea with the compound.
 50. The method of claim 49, wherein the compoundis an alarm odorant ligand.
 51. The method of claim 49, wherein thecompound is a ligand associated with fertility.
 52. The method of claim49, wherein the compound interferes with chemosensory perception.
 53. Acomposition which comprises a compound identified by the method of anyone of claims 27-30, 32-35, or 37-40, and a carrier.
 54. A method ofpreparing a composition which comprises identifying a compound by themethod of any one of claims 27-30, 32-35, or 37-40, recovering thecompound free from the receptor, and admixing a carrier.
 55. A method ofcontrolling a pest population in an area which comprises identifying acompound by the method of claim 27, and spraying the area with thecompound.
 56. The method of claim 55, wherein the compound is a ligandassociated with fertility.